Interferon regulatory factor gene transcriptions: Difference between revisions
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{{AE}} Henry A. Hoff | {{AE}} Henry A. Hoff | ||
Interferon regulatory factors (IRF) are proteins which regulate transcription of [[interferon]]s (see [[regulation of gene expression]]).<ref name="pmid17399883">{{ cite journal |vauthors=Paun A, Pitha PM | title = The IRF family, revisited | journal = Biochimie | volume = 89 | issue = 6–7 | pages = 744–53 | | Interferon regulatory factors (IRF) are proteins which regulate transcription of [[interferon]]s (see [[regulation of gene expression]]).<ref name="pmid17399883">{{ cite journal |vauthors=Paun A, Pitha PM | title = The IRF family, revisited | journal = Biochimie | volume = 89 | issue = 6–7 | pages = 744–53 | date = 2007 | pmid = 17399883 | doi = 10.1016/j.biochi.2007.01.014 }}</ref> They are used in the [[JAK-STAT signaling pathway]].<ref name="IkezuGendelman2008">{{ cite book|author1=Tsuneya Ikezu|author2=Howard E. Gendelman|title=Neuroimmune Pharmacology|url=https://books.google.com/books?id=iGnLjvqvPboC&pg=PA213|accessdate=28 November 2010|date=2008|publisher=Springer|isbn=978-0-387-72572-7|pages=213–}}</ref> Interferon regulatory factors contain a [[conserved sequence|conserved]] [[N-terminal]] region of about 120 [[amino acids]], which [[protein folding|fold]]s into a [[secondary structure|structure]] that binds specifically to the interferon consensus sequence (ICS), which is located [[upstream and downstream (DNA)|upstream]] of the interferon [[gene]]s.<ref name="pmid1460054">{{cite journal |vauthors=Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ | title = Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes | journal = J. Biol. Chem. | volume = 267 | issue = 35 | pages = 25589–96 |date=December 1992 | pmid = 1460054 | doi = | url = }}</ref> The remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein.<ref name="pmid1460054"/> The [[Kaposi sarcoma]] herpesvirus, [[Kaposi's sarcoma-associated herpesvirus|KSHV]]<ref name="pmid7997879">{{cite journal |vauthors=Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS | title = Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma | journal = Science | volume = 266 | issue = 5192 | pages = 1865–9 |date=December 1994 | pmid = 7997879 | doi = 10.1126/science.7997879| bibcode = 1994Sci...266.1865C | url = https://zenodo.org/record/842914}} </ref>, is a cancer virus that encodes four different IRF-like genes<ref name="pmid170897989">{{cite journal |vauthors=Offermann MK | title = Kaposi sarcoma herpesvirus-encoded interferon regulator factors | journal = Curr Top Microbiol Immunol | series = Current Topics in Microbiology and Immunology | volume = 312 | pages = 185–209 |date=2007 | pmid = 17089798 | doi = 10.1007/978-3-540-34344-8_7| isbn = 978-3-540-34343-1 | url = }} </ref>; including vIRF1<ref name="pmid8939871">{{cite journal |vauthors=Moore PS, Boshoff C, Weiss RA, Chang Y | title = Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV | journal = Science | volume = 274 | issue = 5293 | pages = 1739–44 |date=December 1996 | pmid = 8939871 | doi = 10.1126/science.274.5293.1739| bibcode = 1996Sci...274.1739M | ||
| url = }}</ref>, which is a transforming oncoprotein that inhibits type 1 interferon activity.<ref name="pmid9365244">{{cite journal |vauthors=Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS | title = KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway | journal = Oncogene | volume = 15 | issue = 16 | pages = 1979–85 |date=October 1997 | pmid = 9365244 | doi = 10.1038/sj.onc.1201571| url = }}</ref> In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA [[DNA methylation|methylation]]. <ref name="pmid27223861">{{ cite journal |vauthors=Rotondo JC, Borghi A, Selvatici R, Magri E, Bianchini E, Montinari E, Corazza M, Virgili A, Tognon M, Martini F | title = Hypermethylation-Induced Inactivation of the IRF6 Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus | journal = JAMA Dermatology | volume = 152| issue = 8 | pages = 928–33 |date=2016 | pmid = 27223861 | doi = 10.1001/jamadermatol.2016.1336 }}</ref> | |||
==Gene expressions== | ==Gene expressions== | ||
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===IRF1=== | ===IRF1=== | ||
Interferon regulatory factor 1 is a [[protein]] that in humans is encoded by the ''IRF1'' [[gene]].<ref name="pmid2726461">{{cite journal | vauthors = Maruyama M, Fujita T, Taniguchi T | title = Sequence of a cDNA coding for human IRF-1 | journal = Nucleic Acids Res | volume = 17 | issue = 8 | pages = 3292 | date = Jun 1989 | pmid = 2726461 | Interferon regulatory factor 1 is a [[protein]] that in humans is encoded by the ''IRF1'' [[gene]].<ref name="pmid2726461">{{cite journal | vauthors = Maruyama M, Fujita T, Taniguchi T | title = Sequence of a cDNA coding for human IRF-1 | journal = Nucleic Acids Res | volume = 17 | issue = 8 | pages = 3292 | date = Jun 1989 | pmid = 2726461 | ||
| doi = 10.1093/nar/17.8.3292 }}</ref><ref name="pmid1680796">{{cite journal | vauthors = Itoh S, Harada H, Nakamura Y, White R, Taniguchi T | title = Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31 | journal = Genomics | volume = 10 | issue = 4 | pages = 1097–9 | date = Nov 1991 | pmid = 1680796 | |||
| doi = 10.1016/0888-7543(91)90208-V }}</ref> | |||
Interferon regulatory factor 1 was the first member of the [[Interferon regulatory factor|interferon regulatory transcription factor]] (IRF) family identified. Initially described as a transcription factor able to activate expression of the [[cytokine]] [[Interferon beta]],<ref name="Miyamoto M">{{cite journal | vauthors = Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T | title = Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements | journal = Cell | volume = 54 | issue = 6 | pages = 903–13 | date = September 1988 | pmid = 3409321 | doi = 10.1016/S0092-8674(88)91307-4 | Interferon regulatory factor 1 was the first member of the [[Interferon regulatory factor|interferon regulatory transcription factor]] (IRF) family identified. Initially described as a transcription factor able to activate expression of the [[cytokine]] [[Interferon beta]],<ref name="Miyamoto M">{{cite journal | vauthors = Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T | title = Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements | journal = Cell | volume = 54 | issue = 6 | pages = 903–13 | date = September 1988 | pmid = 3409321 | doi = 10.1016/S0092-8674(88)91307-4 }}</ref> IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes. IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their [[Promoter (biology)|promoters]]. The IRF-1 protein binds to the ISRE via an N-terminal [[helix-turn-helix]] DNA binding domain,<ref name="Escalante CR">{{cite journal | vauthors = Escalante CR, Yie J, Thanos D, Aggarwal AK | title = Structure of IRF-1 with bound DNA reveals determinants of interferon regulation | journal = Nature | volume = 391 | issue = 6662 | pages = 103–6 | date = January 1998 | pmid = 9422515 | doi = 10.1038/34224 | bibcode = 1998Natur.391..103E }}</ref> which is highly conserved among all IRF proteins. | ||
Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein [[p53]] through the recruitment of its co-factor [[P300-CBP coactivator family|p300]].<ref name="Dornan D">{{cite journal | vauthors = Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL | title = Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 | journal = Mol. Cell. Biol. | volume = 24 | issue = 22 | pages = 10083–98 | date = November 2004 | pmid = 15509808 | Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein [[p53]] through the recruitment of its co-factor [[P300-CBP coactivator family|p300]].<ref name="Dornan D">{{cite journal | vauthors = Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL | title = Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 | journal = Mol. Cell. Biol. | volume = 24 | issue = 22 | pages = 10083–98 | date = November 2004 | pmid = 15509808 | ||
| doi = 10.1128/MCB.24.22.10083-10098.2004 }}</ref> | |||
IRF-1 has been shown to play roles in the [[immune response]], regulating [[apoptosis]], [[DNA damage]] and [[tumor suppressor gene|tumor suppression]].<ref>{{cite web | title = Entrez Gene: IRF1 interferon regulatory factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3659| accessdate = }}</ref> | IRF-1 has been shown to play roles in the [[immune response]], regulating [[apoptosis]], [[DNA damage]] and [[tumor suppressor gene|tumor suppression]].<ref>{{cite web | title = Entrez Gene: IRF1 interferon regulatory factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3659| accessdate = }}</ref> | ||
It has been shown that the extreme [[C-terminus]] of IRF-1 regulates its ability to activate transcription, [[single-domain antibody|nanobodies]] targeting this domain (MF1) are able to increase IRF-1 activity.<ref name="pmid20817723">{{cite journal | vauthors = Möller A, Pion E, Narayan V, Ball KL | title = Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain | journal = J. Biol. Chem. | volume = 285 | issue = 49 | pages = 38348–61 | date = December 2010 | pmid = 20817723 | It has been shown that the extreme [[C-terminus]] of IRF-1 regulates its ability to activate transcription, [[single-domain antibody|nanobodies]] targeting this domain (MF1) are able to increase IRF-1 activity.<ref name="pmid20817723">{{cite journal | vauthors = Möller A, Pion E, Narayan V, Ball KL | title = Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain | journal = J. Biol. Chem. | volume = 285 | issue = 49 | pages = 38348–61 | date = December 2010 | pmid = 20817723 | ||
| doi = 10.1074/jbc.M110.149476 }}</ref> | |||
===IRF2=== | ===IRF2=== | ||
Interferon regulatory factor 2 is a [[protein]] that in humans is encoded by the ''IRF2'' [[gene]].<ref name="pmid2475256">{{cite journal | vauthors = Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T | title = Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes | journal = Cell | volume = 58 | issue = 4 | pages = 729–39 | date = September 1989 | pmid = 2475256 | Interferon regulatory factor 2 is a [[protein]] that in humans is encoded by the ''IRF2'' [[gene]].<ref name="pmid2475256">{{cite journal | vauthors = Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T | title = Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes | journal = Cell | volume = 58 | issue = 4 | pages = 729–39 | date = September 1989 | pmid = 2475256 | ||
| doi = 10.1016/0092-8674(89)90107-4 }}</ref> | |||
IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the [[IRF1]]-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of [[histone H4]].<ref>{{cite web | title = Entrez Gene: IRF2 interferon regulatory factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3660| accessdate = }}</ref> | IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the [[IRF1]]-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of [[histone H4]].<ref>{{cite web | title = Entrez Gene: IRF2 interferon regulatory factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3660| accessdate = }}</ref> | ||
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===IRF3=== | ===IRF3=== | ||
Interferon regulatory factor 3 (IRF3) is an [[interferon regulatory factor]].<ref name="pmid10048763">{{cite journal | vauthors = Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R | title = Triggering the interferon response: the role of IRF-3 transcription factor | journal = J. Interferon Cytokine Res. | volume = 19 | issue = 1 | pages = 1–13 | | Interferon regulatory factor 3 (IRF3) is an [[interferon regulatory factor]].<ref name="pmid10048763">{{cite journal | vauthors = Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R | title = Triggering the interferon response: the role of IRF-3 transcription factor | journal = J. Interferon Cytokine Res. | volume = 19 | issue = 1 | pages = 1–13 | date = 1999 | pmid = 10048763 | doi = 10.1089/107999099314360 }}</ref> | ||
IRF3 is a member of the interferon regulatory transcription factor (IRF) family.<ref name="pmid10048763"/> IRF3 was originally discovered as a [[homolog]] of [[IRF1]] and [[IRF2]]. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a [[DNA-binding domain]], a [[C-terminal]] IRF association domain and several regulatory [[phosphorylation]] sites.<ref name="Lin-1999">{{cite journal | vauthors = Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J | title = Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription | journal = Mol Cell Biol | volume = 19 | issue = 2 | pages = 959–66 | date = Feb 1999 | pmid = 9891032 | IRF3 is a member of the interferon regulatory transcription factor (IRF) family.<ref name="pmid10048763"/> IRF3 was originally discovered as a [[homolog]] of [[IRF1]] and [[IRF2]]. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a [[DNA-binding domain]], a [[C-terminal]] IRF association domain and several regulatory [[phosphorylation]] sites.<ref name="Lin-1999">{{cite journal | vauthors = Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J | title = Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription | journal = Mol Cell Biol | volume = 19 | issue = 2 | pages = 959–66 | date = Feb 1999 | pmid = 9891032 | ||
| doi = 10.1128/MCB.19.2.959}}</ref> IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with [[CREB binding protein|CREBBP]].<ref name="pmid11846977">{{cite journal | vauthors = Yoneyama M, Suhara W, Fujita T | title = Control of IRF-3 activation by phosphorylation | journal = J. Interferon Cytokine Res. | volume = 22 | issue = 1 | pages = 73–6 | date = 2002 | pmid = 11846977 | doi = 10.1089/107999002753452674 }}</ref> This complex [[Protein targeting#Protein translocation|translocates]] to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes.<ref>{{cite web | title = Entrez Gene: IRF3 interferon regulatory factor 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3661| accessdate = }}</ref> | |||
IRF3 plays an important role in the [[innate immune system]]'s response to [[viral infection]].<ref name="Collins-2004">{{cite journal | vauthors = Collins SE, Noyce RS, Mossman KL | title = Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication | journal = J Virol | volume = 78 | issue = 4 | pages = 1706–17 | date = Feb 2004 | pmid = 14747536 | IRF3 plays an important role in the [[innate immune system]]'s response to [[viral infection]].<ref name="Collins-2004">{{cite journal | vauthors = Collins SE, Noyce RS, Mossman KL | title = Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication | journal = J Virol | volume = 78 | issue = 4 | pages = 1706–17 | date = Feb 2004 | pmid = 14747536 | ||
| doi = 10.1128/JVI.78.4.1706-1717.2004 }}</ref> Aggregated [[VISA (gene)|MAVS]] have been found to activate IRF3 dimerization.<ref>{{cite journal | vauthors = Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ | title = MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response | journal = Cell | volume = 146 | issue = 3 | pages = 448–61 | date = Aug 5, 2011 | pmid = 21782231 | |||
| doi = 10.1016/j.cell.2011.06.041 }}</ref> A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons.<ref>{{cite journal | vauthors = Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ | title = Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. | journal = Science | volume = 347 | issue = 6227 | pages = aaa2630 | date = Mar 13, 2015 | pmid = 25636800 | doi = 10.1126/science.aaa2630 }}</ref> Another study has shown that IRF3-/- knockouts protect from myocardial infarction.<ref name="pmid29106401">{{cite journal | vauthors = King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng Jr RP, Kohler RH, Arlauckas SP, Iwamoto Y, Savol A, Sadreyev RI, Kelly M, Fitzgibbons TP, Fitzgerald KA, Mitchison T, Libby P, Nahrendorf M, Weissleder R | title = IRF3 and type I interferons fuel a fatal response to myocardial infarction. | journal = Nature Medicine | volume = 23 | issue = 12 | pages = 1481–1487 | date = Nov 6, 2017 | pmid = 29106401 | |||
| doi = 10.1038/nm.4428 }}</ref> The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-[[myocardial infarction]] cardioprotection.<ref name="pmid29106401"/> | |||
===IRF4=== | ===IRF4=== | ||
Interferon regulatory factor 4 also known as ''MUM1'' is a [[protein]] that in humans is encoded by the ''IRF4'' [[gene]],<ref name="pmid8921401">{{cite journal | vauthors = Grossman A, Mittrücker HW, Nicholl J, Suzuki A, Chung S, Antonio L, Suggs S, Sutherland GR, Siderovski DP, Mak TW | title = Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25 | journal = Genomics | volume = 37 | issue = 2 | pages = 229–33 | date = Feb 1997 | pmid = 8921401 | Interferon regulatory factor 4 also known as ''MUM1'' is a [[protein]] that in humans is encoded by the ''IRF4'' [[gene]],<ref name="pmid8921401">{{cite journal | vauthors = Grossman A, Mittrücker HW, Nicholl J, Suzuki A, Chung S, Antonio L, Suggs S, Sutherland GR, Siderovski DP, Mak TW | title = Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25 | journal = Genomics | volume = 37 | issue = 2 | pages = 229–33 | date = Feb 1997 | pmid = 8921401 | ||
| doi = 10.1006/geno.1996.0547 }}</ref><ref name="pmid18417578">{{cite journal | vauthors = Xu D, Zhao L, Del Valle L, Miklossy J, Zhang L | title = Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes | journal = J Virol | volume = 82 | issue = 13 | pages = 6251–8 | date = June 2008 | pmid = 18417578 | |||
| doi = 10.1128/JVI.00163-08 }}</ref><ref name= IRF4 >{{cite web | title = Entrez Gene: IRF4 interferon regulatory factor 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3662| accessdate = }}</ref> located at 6p25-p23. | |||
In melanocytic cells the IRF4 gene may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | display-authors = 6 | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | | In melanocytic cells the IRF4 gene may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | display-authors = 6 | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | date = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x }}</ref> IRF4 is a transcription factor that has been implicated in acute leukemia.<ref name="pmid23977280">{{cite journal | vauthors = Adamaki M, Lambrou GI, Athanasiadou A, Tzanoudaki M, Vlahopoulos S, Moschovi M | title = Implication of IRF4 aberrant gene expression in the acute leukemias of childhood | journal = PLOS ONE | volume = 8 | issue = 8 | pages = e72326 | date = 2013 | pmid = 23977280 | ||
| doi = 10.1371/journal.pone.0072326 | bibcode = 2013PLoSO...872326A }}</ref> This gene is strongly associated with pigmentation: sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color.<ref name="pmid24267888">{{cite journal | vauthors = Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, Van Otterloo E, Kim RS, Bergsteinsdottir K, Ogmundsdottir MH, Magnusdottir E, Mishra PJ, Davis SR, Guo T, Zaidi MR, Helgason AS, Sigurdsson MI, Meltzer PS, Merlino G, Petit V, Larue L, Loftus SK, Adams DR, Sobhiafshar U, Emre NC, Pavan WJ, Cornell R, Smith AG, McCallion AS, Fisher DE, Stefansson K, Sturm RA, Steingrimsson E | display-authors = 6 | title = A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway | journal = Cell | volume = 155 | issue = 5 | pages = 1022–33 | date = November 2013 | pmid = 24267888 | doi = 10.1016/j.cell.2013.10.022 }}</ref> A variant has been implicated in greying of hair.<ref name="pmid26926045">{{cite journal | vauthors = Adhikari K, Fontanil T, Cal S, Mendoza-Revilla J, Fuentes-Guajardo M, Chacón-Duque JC, Al-Saadi F, Johansson JA, Quinto-Sanchez M, Acuña-Alonzo V, Jaramillo C, Arias W, Barquera Lozano R, Macín Pérez G, Gómez-Valdés J, Villamil-Ramírez H, Hunemeier T, Ramallo V, Silva de Cerqueira CC, Hurtado M, Villegas V, Granja V, Gallo C, Poletti G, Schuler-Faccini L, Salzano FM, Bortolini MC, Canizales-Quinteros S, Rothhammer F, Bedoya G, Gonzalez-José R, Headon D, López-Otín C, Tobin DJ, Balding D, Ruiz-Linages A | display-authors = 6 | title = A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features | journal = Nature Communications | volume = 7 | pages = 10815 | date = 2016 | pmid = 26926045 | doi = 10.1038/ncomms10815 | lay-url = https://www.bbc.co.uk/news/health-35687287 | laysource = BBC News | |||
| bibcode = 2016NatCo...710815A }}</ref> | |||
===IRF5=== | ===IRF5=== | ||
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IRF5 is a member of the [[interferon regulatory factor]] (IRF) family, a group of [[transcription factor]]s with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved [[N-terminus|N-terminal]] [[DNA-binding domain]] containing [[tryptophan]] (W) repeats. Alternative splice variants encoding different isoforms exist.<ref name= IRF5/> | IRF5 is a member of the [[interferon regulatory factor]] (IRF) family, a group of [[transcription factor]]s with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved [[N-terminus|N-terminal]] [[DNA-binding domain]] containing [[tryptophan]] (W) repeats. Alternative splice variants encoding different isoforms exist.<ref name= IRF5/> | ||
An adaptor protein named TASL plays an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,<ref>{{cite journal |last1=Heinz |first1=Leonhard X. |last2=Lee |first2=JangEun |last3=Kapoor |first3=Utkarsh |last4=Kartnig |first4=Felix |last5=Sedlyarov |first5=Vitaly |last6=Papakostas |first6=Konstantinos |last7=César-Razquin |first7=Adrian |last8=Essletzbichler |first8=Patrick |last9=Goldmann |first9=Ulrich |last10=Stefanovic |first10=Adrijana |last11=Bigenzahn |first11=Johannes W. |last12=Scorzoni |first12=Stefania |last13=Pizzagalli |first13=Mattia D. |last14=Bensimon |first14=Ariel |last15=Müller |first15=André C. |last16=King |first16=F. James |last17=Li |first17=Jun |last18=Girardi |first18=Enrico |last19=Mbow |first19=M. Lamine |last20=Whitehurst |first20=Charles E. |last21=Rebsamen |first21=Manuele |last22=Superti-Furga |first22=Giulio |title=TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7–9 |journal=Nature |date=13 May 2020 |pages=316–322 |doi=10.1038/s41586-020-2282-0 |volume=581 |issue=7808 |pmid=32433612 |bibcode=2020Natur.581..316H | An adaptor protein named TASL plays an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,<ref>{{cite journal |last1=Heinz |first1=Leonhard X. |last2=Lee |first2=JangEun |last3=Kapoor |first3=Utkarsh |last4=Kartnig |first4=Felix |last5=Sedlyarov |first5=Vitaly |last6=Papakostas |first6=Konstantinos |last7=César-Razquin |first7=Adrian |last8=Essletzbichler |first8=Patrick |last9=Goldmann |first9=Ulrich |last10=Stefanovic |first10=Adrijana |last11=Bigenzahn |first11=Johannes W. |last12=Scorzoni |first12=Stefania |last13=Pizzagalli |first13=Mattia D. |last14=Bensimon |first14=Ariel |last15=Müller |first15=André C. |last16=King |first16=F. James |last17=Li |first17=Jun |last18=Girardi |first18=Enrico |last19=Mbow |first19=M. Lamine |last20=Whitehurst |first20=Charles E. |last21=Rebsamen |first21=Manuele |last22=Superti-Furga |first22=Giulio |title=TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7–9 |journal=Nature |date=13 May 2020 |pages=316–322 |doi=10.1038/s41586-020-2282-0 |volume=581 |issue=7808 |pmid=32433612 |bibcode=2020Natur.581..316H }}</ref> drawing a similar analogy to the [[IRF3#Function|IRF3]] activation pathway through the adaptor proteins MAVS, STING and TRIF.<ref>{{cite journal | vauthors = Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ | title = Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. | journal = Science | volume = 347 | issue = 6227 | pages = aaa2630 | date = March 13, 2015 | pmid = 25636800 | doi = 10.1126/science.aaa2630 }}</ref> | ||
===IRF6=== | ===IRF6=== | ||
Interferon regulatory factor 6 (IRF6) is a [[protein]] that in humans is encoded by the ''IRF6'' [[gene]].<ref name="pmid12219090">{{cite journal |vauthors=Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, Moretti-Ferreira D, Richieri-Costa A, Dixon MJ, Murray JC | title = Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes | journal = | Interferon regulatory factor 6 (IRF6) is a [[protein]] that in humans is encoded by the ''IRF6'' [[gene]].<ref name="pmid12219090">{{cite journal |vauthors=Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, Moretti-Ferreira D, Richieri-Costa A, Dixon MJ, Murray JC | title = Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes | journal = Nature Genetics | volume = 32 | issue = 2 | pages = 285–9 |date=October 2002 | pmid = 12219090 | doi = 10.1038/ng985 | url = }}</ref> | ||
This gene encodes a member of the [[interferon regulatory factors|interferon regulatory transcription factor]] (IRF) family. Family members share a highly conserved [[N-terminus|N-terminal]] [[helix-turn-helix]] DNA-binding domain and a less conserved [[C-terminus|C-terminal]] protein-binding domain.<ref name= IRF6 >{{cite web | title = Entrez Gene: IRF6 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3664 | accessdate = }}</ref> The function of IRF6 is related to the formation of [[connective tissue]], for example that of the [[palate]].<ref name="pmid16096995">{{cite journal |vauthors=Blanton SH, Cortez A, Stal S, Mulliken JB, Finnell RH, Hecht JT | title = Variation in IRF6 contributes to nonsyndromic cleft lip and palate | journal = Am. J. Med. Genet. A | volume = 137A | issue = 3 | pages = 259–62 |date=September 2005 | pmid = 16096995 | doi = 10.1002/ajmg.a.30887 | This gene encodes a member of the [[interferon regulatory factors|interferon regulatory transcription factor]] (IRF) family. Family members share a highly conserved [[N-terminus|N-terminal]] [[helix-turn-helix]] DNA-binding domain and a less conserved [[C-terminus|C-terminal]] protein-binding domain.<ref name= IRF6 >{{ cite web | title = Entrez Gene: IRF6 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3664 | accessdate = }}</ref> The function of IRF6 is related to the formation of [[connective tissue]], for example that of the [[palate]].<ref name="pmid16096995">{{cite journal |vauthors=Blanton SH, Cortez A, Stal S, Mulliken JB, Finnell RH, Hecht JT | title = Variation in IRF6 contributes to nonsyndromic cleft lip and palate | journal = Am. J. Med. Genet. A | volume = 137A | issue = 3 | pages = 259–62 |date=September 2005 | pmid = 16096995 | doi = 10.1002/ajmg.a.30887 }}</ref> This gene encodes a member of the [[interferon]] regulatory transcription factor (IRF) family. In addition, it has been observed that IRF6 gene is under epigenetic regulation by promoter [[DNA methylation|methylation]].<ref name="pmid27223861"/> | ||
===IRF7=== | ===IRF7=== | ||
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Interferon regulatory factor 7 (IRF7) is a member of the [[interferon regulatory factor]] family of [[transcription factor]]s. | Interferon regulatory factor 7 (IRF7) is a member of the [[interferon regulatory factor]] family of [[transcription factor]]s. | ||
IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of [[virus-inducible cellular gene]]s, including the [[type I interferon]] genes. In particular, IRF7 regulates many [[interferon-alpha]] genes.<ref name=pmid9822609>{{cite journal | vauthors = Marié I, Durbin JE, Levy DE | title = Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7 | journal = The EMBO Journal | volume = 17 | issue = 22 | pages = 6660–9 | date = November 1998 | pmid = 9822609 | IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of [[virus-inducible cellular gene]]s, including the [[type I interferon]] genes. In particular, IRF7 regulates many [[interferon-alpha]] genes.<ref name=pmid9822609>{{cite journal | vauthors = Marié I, Durbin JE, Levy DE | title = Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7 | journal = The EMBO Journal | volume = 17 | issue = 22 | pages = 6660–9 | date = November 1998 | pmid = 9822609 | ||
| doi = 10.1093/emboj/17.22.6660 }}</ref> Constitutive expression of IRF7 is largely restricted to [[lymphoid tissue]], largely plasmacytoid dendritic cells, whereas IRF7 is inducible in many tissues. Multiple IRF7 transcript variants have been identified, although the functional consequences of these have not yet been established.<ref name= IRF7 >{{cite web | title = Entrez Gene: IRF7 interferon regulatory factor 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3665| access-date = }}</ref> | |||
The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response.<ref>{{cite journal|title=Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape|journal=Nature Medicine|volume=18|issue=8|pages=1224–1231|author=Bidwell| | The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response.<ref>{{ cite journal|title=Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape|journal=Nature Medicine|volume=18|issue=8|pages=1224–1231|author=Bidwell|date=2012|doi=10.1038/nm.2830|pmid=22820642 }}</ref> Restoring IRF7 to these cell lines reduced metastases and increased host survival time in animal models. | ||
The IRF7 gene and product were shown to be defective in a patient with severe susceptibility to H1N1 [[influenza]], while susceptibility to other viral diseases such as CMV, RSV, and [[Human parainfluenza viruses|parainfluenza]] was unaffected.<ref>{{cite journal | vauthors = Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, Israelsson E, Lim HK, Casadio M, Hermesh T, Lorenzo L, Leung LW, Pedergnana V, Boisson B, Okada S, Picard C, Ringuier B, Troussier F, Chaussabel D, Abel L, Pellier I, Notarangelo LD, García-Sastre A, Basler CF, Geissmann F, Zhang SY, Snoeck HW, Casanova JL | title = Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency | journal = Science | volume = 348 | issue = 6233 | pages = 448–53 | date = April 2015 | pmid = 25814066 | The IRF7 gene and product were shown to be defective in a patient with severe susceptibility to H1N1 [[influenza]], while susceptibility to other viral diseases such as CMV, RSV, and [[Human parainfluenza viruses|parainfluenza]] was unaffected.<ref>{{cite journal | vauthors = Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, Israelsson E, Lim HK, Casadio M, Hermesh T, Lorenzo L, Leung LW, Pedergnana V, Boisson B, Okada S, Picard C, Ringuier B, Troussier F, Chaussabel D, Abel L, Pellier I, Notarangelo LD, García-Sastre A, Basler CF, Geissmann F, Zhang SY, Snoeck HW, Casanova JL | title = Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency | journal = Science | volume = 348 | issue = 6233 | pages = 448–53 | date = April 2015 | pmid = 25814066 | ||
| doi = 10.1126/science.aaa1578 }}</ref> | |||
===IRF8=== | ===IRF8=== | ||
Interferon regulatory factor 8 (IRF8) also known as the interferon consensus sequence-binding protein (ICSBP), is a [[protein]] that in humans is encoded by the ''IRF8'' [[gene]].<ref name= IRF8 >{{cite web | title = Entrez Gene: IRF8 interferon regulatory factor 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3394| accessdate = }}</ref><ref name="pmid1460054"/><ref name="pmid11997525">{{cite journal | vauthors = Nehyba J, Hrdlicková R, Burnside J, Bose HR | title = A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein | journal = Mol. Cell. Biol. | volume = 22 | issue = 11 | pages = 3942–57 | date = June 2002 | pmid = 11997525 | Interferon regulatory factor 8 (IRF8) also known as the interferon consensus sequence-binding protein (ICSBP), is a [[protein]] that in humans is encoded by the ''IRF8'' [[gene]].<ref name= IRF8 >{{ cite web | title = Entrez Gene: IRF8 interferon regulatory factor 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3394| accessdate = }}</ref><ref name="pmid1460054"/><ref name="pmid11997525">{{ cite journal | vauthors = Nehyba J, Hrdlicková R, Burnside J, Bose HR | title = A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein | journal = Mol. Cell. Biol. | volume = 22 | issue = 11 | pages = 3942–57 | date = June 2002 | pmid = 11997525 | ||
| doi = 10.1128/MCB.22.11.3942-3957.2002 }}</ref> IRF8 is a [[transcription factor]] that plays critical roles in the regulation of lineage commitment and in [[myeloid]] [[Cell (biology)|cell]] maturation including the decision for a common myeloid progenitor (CMP) to [[Cellular differentiation|differentiate]] into a [[monocyte]] precursor cell. | |||
[[Interferon Consensus Sequence-binding protein]] (ICSBP) is a [[transcription factor]] of the [[interferon]] regulatory factor ([[Interferon regulatory factors|IRF]]) family. Proteins of this family are composed of a conserved [[DNA-binding domain]] in the [[N-terminus|N-terminal]] region and a divergent [[C-terminus|C-terminal]] region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated [[response element]] (ISRE) and regulate expression of genes stimulated by type I IFNs, namely [[Interferon type I#IFN-.CE.B1|IFN-α]] and [[Interferon type I#IFN-.CE.B2|IFN-β]]. IRF family proteins also control expression of IFN-α and IFN-β-regulated genes that are induced by viral infection.<ref name= IRF8/> | [[Interferon Consensus Sequence-binding protein]] (ICSBP) is a [[transcription factor]] of the [[interferon]] regulatory factor ([[Interferon regulatory factors|IRF]]) family. Proteins of this family are composed of a conserved [[DNA-binding domain]] in the [[N-terminus|N-terminal]] region and a divergent [[C-terminus|C-terminal]] region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated [[response element]] (ISRE) and regulate expression of genes stimulated by type I IFNs, namely [[Interferon type I#IFN-.CE.B1|IFN-α]] and [[Interferon type I#IFN-.CE.B2|IFN-β]]. IRF family proteins also control expression of IFN-α and IFN-β-regulated genes that are induced by viral infection.<ref name= IRF8/> | ||
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===IRF9=== | ===IRF9=== | ||
Interferon regulatory factor 9 is a [[protein]] that in humans is encoded by the ''IRF9'' [[gene]], previously known as ISGF3G.<ref name="pmid1630447">{{cite journal |vauthors=Veals SA, Schindler C, Leonard D, Fu XY, Aebersold R, ((Darnell JE Jr)), Levy DE | title = Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins | journal = Mol Cell Biol | volume = 12 | issue = 8 | pages = 3315–24 |date= | Interferon regulatory factor 9 is a [[protein]] that in humans is encoded by the ''IRF9'' [[gene]], previously known as ISGF3G.<ref name="pmid1630447">{{ cite journal |vauthors=Veals SA, Schindler C, Leonard D, Fu XY, Aebersold R, ((Darnell JE Jr)), Levy DE | title = Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins | journal = Mol Cell Biol | volume = 12 | issue = 8 | pages = 3315–24 |date=August 1992 | pmid = 1630447 | ||
| doi = 10.1128/MCB.12.8.3315}}</ref><ref name="pmid10199920">{{cite journal |vauthors=McCusker D, Wilson M, Trowsdale J | title = Organization of the genes encoding the human proteasome activators PA28alpha and beta | journal = Immunogenetics | volume = 49 | issue = 5 | pages = 438–45 |date=June 1999 | pmid = 10199920 | |||
| doi =10.1007/s002510050517 }}</ref><ref name= ISGF3G >{{ cite web | title = Entrez Gene: ISGF3G interferon-stimulated transcription factor 3, gamma 48kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10379| accessdate = }}</ref> | |||
==Interactions== | ==Interactions== | ||
{{main|Interaction gene transcriptions}} | {{main|Interaction gene transcriptions}} | ||
IRF1 has been shown to [[Protein-protein interaction|interact]] with: | IRF1 has been shown to [[Protein-protein interaction|interact]] with: | ||
* [[STUB1|CHIP]]<ref name="pmid20947504">{{cite journal | vauthors = Narayan V, Pion E, Landré V, Müller P, Ball KL | title = Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP | journal = J Biol Chem | volume = 286 | issue = 1 | pages = 607–19 | date = October 2010 | pmid = 20947504 | * [[STUB1|CHIP]]<ref name="pmid20947504">{{cite journal | vauthors = Narayan V, Pion E, Landré V, Müller P, Ball KL | title = Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP | journal = J Biol Chem | volume = 286 | issue = 1 | pages = 607–19 | date = October 2010 | pmid = 20947504 | ||
| doi = 10.1074/jbc.M110.153122 }}</ref> | |||
* [[GAGE]]<ref name="pmid19642896">{{cite journal | vauthors = Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R, Deiss LP | title = GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1 | journal = J. Interferon Cytokine Res. | volume = 29 | issue = 10 | pages = 645–55 | date = October 2009 | pmid = 19642896 | doi = 10.1089/jir.2008.0099 }}</ref> | * [[GAGE]]<ref name="pmid19642896">{{cite journal | vauthors = Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R, Deiss LP | title = GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1 | journal = J. Interferon Cytokine Res. | volume = 29 | issue = 10 | pages = 645–55 | date = October 2009 | pmid = 19642896 | doi = 10.1089/jir.2008.0099 }}</ref> | ||
* [[HSP70]] / [[HSP90]]<ref name="pmid19502235">{{cite journal | vauthors = Narayan V, Eckert M, Zylicz A, Zylicz M, Ball KL | title = Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery | journal = J Biol Chem | volume = 284 | issue = 38 | pages = 25889–99 | date = September 2009 | pmid = 19502235 | * [[HSP70]] / [[HSP90]]<ref name="pmid19502235">{{cite journal | vauthors = Narayan V, Eckert M, Zylicz A, Zylicz M, Ball KL | title = Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery | journal = J Biol Chem | volume = 284 | issue = 38 | pages = 25889–99 | date = September 2009 | pmid = 19502235 | ||
* [[IRF8]]<ref name="pmid9742224">{{cite journal | vauthors = Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H | title = Functional domains of interferon regulatory factor I (IRF-1) | journal = Biochem. J. | volume = 335 | issue = 1 | pages = 147–57 | date = October 1998 | pmid = 9742224 | | doi = 10.1074/jbc.M109.019505 }}</ref> | ||
* [[IRF8]]<ref name="pmid9742224">{{cite journal | vauthors = Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H | title = Functional domains of interferon regulatory factor I (IRF-1) | journal = Biochem. J. | volume = 335 | issue = 1 | pages = 147–57 | date = October 1998 | pmid = 9742224 | |||
| doi = 10.1042/bj3350147}}</ref><ref name="pmid7768900">{{cite journal | vauthors = Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ | title = Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13063–9 | date = June 1995 | pmid = 7768900 | doi = 10.1074/jbc.270.22.13063 }}</ref> | |||
* [[KPNA2]]<ref name="pmid17255955">{{cite journal | vauthors = Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, Katayama I, Kaneda Y | title = Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1 | journal = J. Invest. Dermatol. | volume = 127 | issue = 6 | pages = 1456–64 | date = June 2007 | pmid = 17255955 | doi = 10.1038/sj.jid.5700716 }}</ref> | * [[KPNA2]]<ref name="pmid17255955">{{cite journal | vauthors = Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, Katayama I, Kaneda Y | title = Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1 | journal = J. Invest. Dermatol. | volume = 127 | issue = 6 | pages = 1456–64 | date = June 2007 | pmid = 17255955 | doi = 10.1038/sj.jid.5700716 }}</ref> | ||
* [[MYD88]]<ref name="pmid17018642">{{cite journal | vauthors = Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K | title = Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program | journal = | * [[MYD88]]<ref name="pmid17018642">{{cite journal | vauthors = Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K | title = Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program | journal = Proceedings of the National Academy of Science U.S.A. | volume = 103 | issue = 41 | pages = 15136–41 | date = October 2006 | pmid = 17018642 | ||
* [[PCAF]]<ref name="pmid10022868">{{cite journal | vauthors = Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K | title = The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness | journal = Mol. Cell. Biol. | volume = 19 | issue = 3 | pages = 1810–20 | date = March 1999 | pmid = 10022868 | | doi = 10.1073/pnas.0607181103 | bibcode = 2006PNAS..10315136N }}</ref> | ||
* [[STAT1]]<ref name="pmid10764778">{{cite journal | vauthors = Chatterjee-Kishore M, van Den Akker F, Stark GR | title = Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1 | journal = | * [[PCAF]]<ref name="pmid10022868">{{cite journal | vauthors = Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K | title = The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness | journal = Mol. Cell. Biol. | volume = 19 | issue = 3 | pages = 1810–20 | date = March 1999 | pmid = 10022868 | ||
* [[Tat (HIV)|TAT]]<ref name="pmid12021315">{{cite journal | vauthors = Sgarbanti M, Borsetti A, Moscufo N, Bellocchi MC, Ridolfi B, Nappi F, Marsili G, Marziali G, Coccia EM, Ensoli B, Battistini A | title = Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors | journal = J. Exp. Med. | volume = 195 | issue = 10 | pages = 1359–70 | date = May 2002 | pmid = 12021315 | | doi = 10.1128/MCB.19.3.1810}}</ref> | ||
* [[STAT1]]<ref name="pmid10764778">{{cite journal | vauthors = Chatterjee-Kishore M, van Den Akker F, Stark GR | title = Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1 | journal = Journal Biol. Chem. | volume = 275 | issue = 27 | pages = 20406–11 | date = July 2000 | pmid = 10764778 | doi = 10.1074/jbc.M001861200 }}</ref> | |||
* [[Tat (HIV)|TAT]]<ref name="pmid12021315">{{cite journal | vauthors = Sgarbanti M, Borsetti A, Moscufo N, Bellocchi MC, Ridolfi B, Nappi F, Marsili G, Marziali G, Coccia EM, Ensoli B, Battistini A | title = Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors | journal = J. Exp. Med. | volume = 195 | issue = 10 | pages = 1359–70 | date = May 2002 | pmid = 12021315 | |||
| doi = 10.1084/jem.20010753 }}</ref> | |||
* [[VEGFR2]]<ref name="pmid18472010">{{cite journal | vauthors = Lee JH, Chun T, Park SY, Rho SB | title = Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs | journal = Biochim. Biophys. Acta | volume = 1783 | issue = 9 | pages = 1654–62 | date = September 2008 | pmid = 18472010 | doi = 10.1016/j.bbamcr.2008.04.006 }}</ref> | * [[VEGFR2]]<ref name="pmid18472010">{{cite journal | vauthors = Lee JH, Chun T, Park SY, Rho SB | title = Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs | journal = Biochim. Biophys. Acta | volume = 1783 | issue = 9 | pages = 1654–62 | date = September 2008 | pmid = 18472010 | doi = 10.1016/j.bbamcr.2008.04.006 }}</ref> | ||
* REDD2<ref>{{Cite journal|last1=Gupta|first1=M.|last2=Rath|first2=PC| | * REDD2<ref>{{Cite journal|last1=Gupta|first1=M.|last2=Rath|first2=PC|date=2014|title=Interferon regulatory factor-1 (IRF-1) interacts with regulated in development and DNA damage response 2 (REDD2) in the cytoplasm of mouse bone marrow cells.|journal=Int J Biol Macromol.|volume=65|pages=41–50|doi=10.1016/j.ijbiomac.2014.01.005|pmid=24412152}}</ref> | ||
IRF2 has been shown to [[Protein-protein interaction|interact]] with [[BRD7]],<ref name=pmid11025449>{{cite journal | vauthors = Staal A, Enserink JM, Stein JL, Stein GS, van Wijnen AJ | title = Molecular characterization of celtix-1, a bromodomain protein interacting with the transcription factor interferon regulatory factor 2 | journal = J. Cell. | IRF2 has been shown to [[Protein-protein interaction|interact]] with [[BRD7]],<ref name=pmid11025449>{{ cite journal | vauthors = Staal A, Enserink JM, Stein JL, Stein GS, van Wijnen AJ | title = Molecular characterization of celtix-1, a bromodomain protein interacting with the transcription factor interferon regulatory factor 2 | journal = J. Cell. Physiology | volume = 185 | issue = 2 | pages = 269–79 | date = November 2000 | pmid = 11025449 | doi = 10.1002/1097-4652(200011)185:2<269::AID-JCP12>3.0.CO;2-L }}</ref> [[EP300]]<ref name=pmid11304541>{{cite journal | vauthors = Masumi A, Ozato K | title = Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment | journal = Journal of Biol. Chemistry | volume = 276 | issue = 24 | pages = 20973–80 | date = June 2001 | pmid = 11304541 | doi = 10.1074/jbc.M101707200 }}</ref> and [[PCAF]].<ref name=pmid11304541/><ref name=pmid10022868/> | ||
IRF3 has been shown to [[Protein-protein interaction|interact]] with [[IRF7]].<ref name=pmid11162841>{{cite journal | vauthors = Au WC, Yeow WS, Pitha PM | title = Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3 | journal = Virology | volume = 280 | issue = 2 | pages = 273–82 | date = | IRF3 has been shown to [[Protein-protein interaction|interact]] with [[IRF7]].<ref name=pmid11162841>{{cite journal | vauthors = Au WC, Yeow WS, Pitha PM | title = Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3 | journal = Virology | volume = 280 | issue = 2 | pages = 273–82 | date = February 2001 | pmid = 11162841 | doi = 10.1006/viro.2000.0782 }}</ref> | ||
IRF4 has been shown to [[Protein-protein interaction|interact]] with: | IRF4 has been shown to [[Protein-protein interaction|interact]] with: | ||
* [[BCL6]],<ref name=pmid10601358/> | * [[BCL6]],<ref name=pmid10601358/> | ||
* [[NFATC2]],<ref name="pmid11956291">{{cite journal | vauthors = Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH | title = Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression | journal = J. Exp. Med. | volume = 195 | issue = 8 | pages = 1003–12 | date = April 2002 | pmid = 11956291 | * [[NFATC2]],<ref name="pmid11956291">{{cite journal | vauthors = Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH | title = Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression | journal = J. Exp. Med. | volume = 195 | issue = 8 | pages = 1003–12 | date = April 2002 | pmid = 11956291 | ||
* [[SPI1]],<ref name="pmid10022840">{{cite journal | vauthors = Brass AL, Zhu AQ, Singh H | title = Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers | journal = EMBO J. | volume = 18 | issue = 4 | pages = 977–91 | date = February 1999 | pmid = 10022840 | | doi = 10.1084/jem.20011128 }}</ref> | ||
* [[STAT6]].<ref name="pmid10601358">{{cite journal | vauthors = Gupta S, Jiang M, Anthony A, Pernis AB | title = Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4 | journal = | * [[SPI1]],<ref name="pmid10022840">{{cite journal | vauthors = Brass AL, Zhu AQ, Singh H | title = Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers | journal = EMBO J. | volume = 18 | issue = 4 | pages = 977–91 | date = February 1999 | pmid = 10022840 | ||
| doi = 10.1093/emboj/18.4.977 }}</ref><ref name="pmid12372320">{{ cite journal | vauthors = Escalante CR, Shen L, Escalante MC, Brass AL, Edwards TA, Singh H, Aggarwal AK | title = Crystallization and characterization of PU.1/IRF-4/DNA ternary complex | journal = Journal of Struct. Biol. | volume = 139 | issue = 1 | pages = 55–9 | date = July 2002 | pmid = 12372320 | doi = 10.1016/S1047-8477(02)00514-2 }}</ref> and | |||
* [[STAT6]].<ref name="pmid10601358">{{cite journal | vauthors = Gupta S, Jiang M, Anthony A, Pernis AB | title = Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4 | journal = Journal of Exp. Med. | volume = 190 | issue = 12 | pages = 1837–48 | date = December 1999 | pmid = 10601358 | |||
| doi = 10.1084/jem.190.12.1837 }}</ref> | |||
IRF7 has been shown to [[Protein-protein interaction|interact]] with [[IRF3]].<ref name=pmid11162841/> Also, IRF7 has been shown to interact with [[AH receptor-interacting protein|Aryl Hydrocarbon Receptor Interacting Protein (AIP)]], which is a negative regulator for the antiviral pathway.<ref>{{cite journal | vauthors = Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW | title = Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon | journal = The Journal of Biological Chemistry | volume = 290 | issue = 23 | pages = 14729–39 | date = June 2015 | pmid = 25911105 | doi = 10.1074/jbc.M114.633065 | IRF7 has been shown to [[Protein-protein interaction|interact]] with [[IRF3]].<ref name=pmid11162841/> Also, IRF7 has been shown to interact with [[AH receptor-interacting protein|Aryl Hydrocarbon Receptor Interacting Protein (AIP)]], which is a negative regulator for the antiviral pathway.<ref>{{cite journal | vauthors = Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW | title = Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon | journal = The Journal of Biological Chemistry | volume = 290 | issue = 23 | pages = 14729–39 | date = June 2015 | pmid = 25911105 | doi = 10.1074/jbc.M114.633065 }}</ref> | ||
IRF8 has been shown to [[Protein-protein interaction|interact]] with [[IRF1]]<ref name="pmid9742224"/><ref name="pmid7768900"/> and [[COPS2]].<ref name="pmid10991940">{{cite journal | vauthors = Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W, Levi BZ | title = Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome | journal = | IRF8 has been shown to [[Protein-protein interaction|interact]] with [[IRF1]]<ref name="pmid9742224"/><ref name="pmid7768900"/> and [[COPS2]].<ref name="pmid10991940">{{cite journal | vauthors = Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W, Levi BZ | title = Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome | journal = Journal Biol. Chemistry | volume = 275 | issue = 50 | pages = 39081–9 | date = December 2000 | pmid = 10991940 | doi = 10.1074/jbc.M004900200 }}</ref> | ||
IRF9 has been shown to [[Protein-protein interaction|interact]] with [[STAT2]]<ref name=pmid8943351>{{cite journal |last=Horvath |first=C M |author2=Stark G R |author3=Kerr I M |author4=Darnell J E | IRF9 has been shown to [[Protein-protein interaction|interact]] with [[STAT2]]<ref name=pmid8943351>{{cite journal |last=Horvath |first=C M |author2=Stark G R |author3=Kerr I M |author4=Darnell J E | ||
|date=December 1996 | |||
|title=Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex |journal=Mol. Cell. Biology |volume=16 |issue=12 |pages=6957–64 |location = UNITED STATES | |||
| pmid = 8943351 | |||
| doi=10.1128/mcb.16.12.6957}}</ref><ref name=pmid9242679>{{ cite journal |last=Martinez-Moczygemba |first=M |author2=Gutch M J |author3=French D L |author4=Reich N C |date=Aug 1997 |title=Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3 |journal=J. Biol. Chem. |volume=272 |issue=32 |pages=20070–6 |location = UNITED STATES | |||
| pmid = 9242679 | doi = 10.1074/jbc.272.32.20070 }}</ref> and [[STAT1]].<ref name=pmid8943351/> | |||
==Consensus sequences== | ==Consensus sequences== | ||
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* [[A1BG gene transcriptions]] | * [[A1BG gene transcriptions]] | ||
* [[A1BG regulatory elements and regions]] | |||
* [[Complex locus A1BG and ZNF497]] | * [[Complex locus A1BG and ZNF497]] | ||
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[[Category:Resources last modified in | [[Category:Resources last modified in January 2021]] | ||
Revision as of 01:13, 30 January 2021
Associate Editor(s)-in-Chief: Henry A. Hoff
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression).[1] They are used in the JAK-STAT signaling pathway.[2] Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the interferon consensus sequence (ICS), which is located upstream of the interferon genes.[3] The remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein.[3] The Kaposi sarcoma herpesvirus, KSHV[4], is a cancer virus that encodes four different IRF-like genes[5]; including vIRF1[6], which is a transforming oncoprotein that inhibits type 1 interferon activity.[7] In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation. [8]
Gene expressions
IRF1
Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene.[9][10]
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta,[11] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes. IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their promoters. The IRF-1 protein binds to the ISRE via an N-terminal helix-turn-helix DNA binding domain,[12] which is highly conserved among all IRF proteins.
Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein p53 through the recruitment of its co-factor p300.[13]
IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumor suppression.[14]
It has been shown that the extreme C-terminus of IRF-1 regulates its ability to activate transcription, nanobodies targeting this domain (MF1) are able to increase IRF-1 activity.[15]
IRF2
Interferon regulatory factor 2 is a protein that in humans is encoded by the IRF2 gene.[16]
IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4.[17]
IRF3
Interferon regulatory factor 3 (IRF3) is an interferon regulatory factor.[18]
IRF3 is a member of the interferon regulatory transcription factor (IRF) family.[18] IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites.[19] IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP.[20] This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes.[21]
IRF3 plays an important role in the innate immune system's response to viral infection.[22] Aggregated MAVS have been found to activate IRF3 dimerization.[23] A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons.[24] Another study has shown that IRF3-/- knockouts protect from myocardial infarction.[25] The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-myocardial infarction cardioprotection.[25]
IRF4
Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene,[26][27][28] located at 6p25-p23.
In melanocytic cells the IRF4 gene may be regulated by MITF.[29] IRF4 is a transcription factor that has been implicated in acute leukemia.[30] This gene is strongly associated with pigmentation: sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color.[31] A variant has been implicated in greying of hair.[32]
IRF5
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.[33]
IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist.[33]
An adaptor protein named TASL plays an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,[34] drawing a similar analogy to the IRF3 activation pathway through the adaptor proteins MAVS, STING and TRIF.[35]
IRF6
Interferon regulatory factor 6 (IRF6) is a protein that in humans is encoded by the IRF6 gene.[36]
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain.[37] The function of IRF6 is related to the formation of connective tissue, for example that of the palate.[38] This gene encodes a member of the interferon regulatory transcription factor (IRF) family. In addition, it has been observed that IRF6 gene is under epigenetic regulation by promoter methylation.[8]
IRF7
Interferon regulatory factor 7 (IRF7) is a member of the interferon regulatory factor family of transcription factors.
IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes.[39] Constitutive expression of IRF7 is largely restricted to lymphoid tissue, largely plasmacytoid dendritic cells, whereas IRF7 is inducible in many tissues. Multiple IRF7 transcript variants have been identified, although the functional consequences of these have not yet been established.[40]
The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response.[41] Restoring IRF7 to these cell lines reduced metastases and increased host survival time in animal models.
The IRF7 gene and product were shown to be defective in a patient with severe susceptibility to H1N1 influenza, while susceptibility to other viral diseases such as CMV, RSV, and parainfluenza was unaffected.[42]
IRF8
Interferon regulatory factor 8 (IRF8) also known as the interferon consensus sequence-binding protein (ICSBP), is a protein that in humans is encoded by the IRF8 gene.[43][3][44] IRF8 is a transcription factor that plays critical roles in the regulation of lineage commitment and in myeloid cell maturation including the decision for a common myeloid progenitor (CMP) to differentiate into a monocyte precursor cell.
Interferon Consensus Sequence-binding protein (ICSBP) is a transcription factor of the interferon regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-α and IFN-β. IRF family proteins also control expression of IFN-α and IFN-β-regulated genes that are induced by viral infection.[43]
IRF9
Interferon regulatory factor 9 is a protein that in humans is encoded by the IRF9 gene, previously known as ISGF3G.[45][46][47]
Interactions
IRF1 has been shown to interact with:
- CHIP[48]
- GAGE[49]
- HSP70 / HSP90[50]
- IRF8[51][52]
- KPNA2[53]
- MYD88[54]
- PCAF[55]
- STAT1[56]
- TAT[57]
- VEGFR2[58]
- REDD2[59]
IRF2 has been shown to interact with BRD7,[60] EP300[61] and PCAF.[61][55]
IRF3 has been shown to interact with IRF7.[62]
IRF4 has been shown to interact with:
IRF7 has been shown to interact with IRF3.[62] Also, IRF7 has been shown to interact with Aryl Hydrocarbon Receptor Interacting Protein (AIP), which is a negative regulator for the antiviral pathway.[67]
IRF8 has been shown to interact with IRF1[51][52] and COPS2.[68]
IRF9 has been shown to interact with STAT2[69][70] and STAT1.[69]
Consensus sequences
Consensus sequence for IRF-3 is 5'-GCTTTCC-3'.[71]
Acknowledgements
The content on this page was first contributed by: Henry A. Hoff.
Initial content for this page in some instances came from Wikipedia.
See also
References
- ↑ Paun A, Pitha PM (2007). "The IRF family, revisited". Biochimie. 89 (6–7): 744–53. doi:10.1016/j.biochi.2007.01.014. PMID 17399883.
- ↑ Tsuneya Ikezu; Howard E. Gendelman (2008). Neuroimmune Pharmacology. Springer. pp. 213–. ISBN 978-0-387-72572-7. Retrieved 28 November 2010.
- ↑ 3.0 3.1 3.2 Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (December 1992). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes". J. Biol. Chem. 267 (35): 25589–96. PMID 1460054.
- ↑ Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (December 1994). "Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma". Science. 266 (5192): 1865–9. Bibcode:1994Sci...266.1865C. doi:10.1126/science.7997879. PMID 7997879.
- ↑ Offermann MK (2007). "Kaposi sarcoma herpesvirus-encoded interferon regulator factors". Curr Top Microbiol Immunol. Current Topics in Microbiology and Immunology. 312: 185–209. doi:10.1007/978-3-540-34344-8_7. ISBN 978-3-540-34343-1. PMID 17089798.
- ↑ Moore PS, Boshoff C, Weiss RA, Chang Y (December 1996). "Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV". Science. 274 (5293): 1739–44. Bibcode:1996Sci...274.1739M. doi:10.1126/science.274.5293.1739. PMID 8939871.
- ↑ Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS (October 1997). "KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway". Oncogene. 15 (16): 1979–85. doi:10.1038/sj.onc.1201571. PMID 9365244.
- ↑ 8.0 8.1 Rotondo JC, Borghi A, Selvatici R, Magri E, Bianchini E, Montinari E, Corazza M, Virgili A, Tognon M, Martini F (2016). "Hypermethylation-Induced Inactivation of the IRF6 Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus". JAMA Dermatology. 152 (8): 928–33. doi:10.1001/jamadermatol.2016.1336. PMID 27223861.
- ↑ Maruyama M, Fujita T, Taniguchi T (Jun 1989). "Sequence of a cDNA coding for human IRF-1". Nucleic Acids Res. 17 (8): 3292. doi:10.1093/nar/17.8.3292. PMID 2726461.
- ↑ Itoh S, Harada H, Nakamura Y, White R, Taniguchi T (Nov 1991). "Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31". Genomics. 10 (4): 1097–9. doi:10.1016/0888-7543(91)90208-V. PMID 1680796.
- ↑ Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (September 1988). "Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements". Cell. 54 (6): 903–13. doi:10.1016/S0092-8674(88)91307-4. PMID 3409321.
- ↑ Escalante CR, Yie J, Thanos D, Aggarwal AK (January 1998). "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation". Nature. 391 (6662): 103–6. Bibcode:1998Natur.391..103E. doi:10.1038/34224. PMID 9422515.
- ↑ Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL (November 2004). "Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53". Mol. Cell. Biol. 24 (22): 10083–98. doi:10.1128/MCB.24.22.10083-10098.2004. PMID 15509808.
- ↑ "Entrez Gene: IRF1 interferon regulatory factor 1".
- ↑ Möller A, Pion E, Narayan V, Ball KL (December 2010). "Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain". J. Biol. Chem. 285 (49): 38348–61. doi:10.1074/jbc.M110.149476. PMID 20817723.
- ↑ Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T (September 1989). "Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes". Cell. 58 (4): 729–39. doi:10.1016/0092-8674(89)90107-4. PMID 2475256.
- ↑ "Entrez Gene: IRF2 interferon regulatory factor 2".
- ↑ 18.0 18.1 Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). "Triggering the interferon response: the role of IRF-3 transcription factor". J. Interferon Cytokine Res. 19 (1): 1–13. doi:10.1089/107999099314360. PMID 10048763.
- ↑ Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J (Feb 1999). "Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription". Mol Cell Biol. 19 (2): 959–66. doi:10.1128/MCB.19.2.959. PMID 9891032.
- ↑ Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
- ↑ "Entrez Gene: IRF3 interferon regulatory factor 3".
- ↑ Collins SE, Noyce RS, Mossman KL (Feb 2004). "Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication". J Virol. 78 (4): 1706–17. doi:10.1128/JVI.78.4.1706-1717.2004. PMID 14747536.
- ↑ Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). "MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response". Cell. 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMID 21782231.
- ↑ Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ (Mar 13, 2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation". Science. 347 (6227): aaa2630. doi:10.1126/science.aaa2630. PMID 25636800.
- ↑ 25.0 25.1 King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng Jr RP, Kohler RH, Arlauckas SP, Iwamoto Y, Savol A, Sadreyev RI, Kelly M, Fitzgibbons TP, Fitzgerald KA, Mitchison T, Libby P, Nahrendorf M, Weissleder R (Nov 6, 2017). "IRF3 and type I interferons fuel a fatal response to myocardial infarction". Nature Medicine. 23 (12): 1481–1487. doi:10.1038/nm.4428. PMID 29106401.
- ↑ Grossman A, Mittrücker HW, Nicholl J, Suzuki A, Chung S, Antonio L, Suggs S, Sutherland GR, Siderovski DP, Mak TW (Feb 1997). "Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25". Genomics. 37 (2): 229–33. doi:10.1006/geno.1996.0547. PMID 8921401.
- ↑ Xu D, Zhao L, Del Valle L, Miklossy J, Zhang L (June 2008). "Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes". J Virol. 82 (13): 6251–8. doi:10.1128/JVI.00163-08. PMID 18417578.
- ↑ "Entrez Gene: IRF4 interferon regulatory factor 4".
- ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ Adamaki M, Lambrou GI, Athanasiadou A, Tzanoudaki M, Vlahopoulos S, Moschovi M (2013). "Implication of IRF4 aberrant gene expression in the acute leukemias of childhood". PLOS ONE. 8 (8): e72326. Bibcode:2013PLoSO...872326A. doi:10.1371/journal.pone.0072326. PMID 23977280.
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