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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{AE}} Henry A. Hoff
{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''Transcription factor E2F4''' is a [[protein]] that in humans is encoded by the ''E2F4'' [[gene]].<ref name="pmid7958924">{{cite journal | vauthors = Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM | title = E2F-4, a new member of the E2F transcription factor family, interacts with p107 | journal = Genes Dev | volume = 8 | issue = 22 | pages = 2665–79 |date=Dec 1994 | pmid = 7958924 | pmc =  | doi =10.1101/gad.8.22.2665  }}</ref><ref name="pmid7892279">{{cite journal | vauthors = Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA | title = E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle | journal = Proc Natl Acad Sci U S A | volume = 92 | issue = 6 | pages = 2403–7 |date=Apr 1995 | pmid = 7892279 | pmc = 42492 | doi =10.1073/pnas.92.6.2403  }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_E2F4_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1cf7.
| PDB = {{PDB2|1cf7}}
| Name = E2F transcription factor 4, p107/p130-binding
| HGNCid = 3118
| Symbol = E2F4
| AltSymbols =; E2F-4
| OMIM = 600659
| ECnumber = 
| Homologene = 1471
| MGIid = 103012
| GeneAtlas_image1 = PBB_GE_E2F4_38707_r_at_tn.png
| GeneAtlas_image2 = PBB_GE_E2F4_202248_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005667 |text = transcription factor complex}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007049 |text = cell cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1874
    | Hs_Ensembl = ENSG00000205250
    | Hs_RefseqProtein = NP_001941
    | Hs_RefseqmRNA = NM_001950
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 65783569
    | Hs_GenLoc_end = 65790322
    | Hs_Uniprot = Q16254
    | Mm_EntrezGene = 104394
    | Mm_Ensembl = ENSMUSG00000014859
    | Mm_RefseqmRNA = NM_148952
    | Mm_RefseqProtein = NP_683754
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 108186792
    | Mm_GenLoc_end = 108194499
    | Mm_Uniprot =
  }}
}}
'''E2F transcription factor 4, p107/p130-binding''', also known as '''E2F4''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Gene ID: 1874 E2F transcription factor 4, "The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer."<ref name=RefSeqJuly2008>{{ cite web
{{PBB_Summary
|author=RefSeqJuly2008
| section_title =
|title=E2F4 E2F transcription factor 4 [ Homo sapiens (human) ]
| summary_text = The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer.<ref name="entrez">{{cite web | title = Entrez Gene: E2F4 E2F transcription factor 4, p107/p130-binding| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1874| accessdate = }}</ref>
|publisher=National Center for Biotechnology Information
}}
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=25 December 2016
|url=https://www.ncbi.nlm.nih.gov/gene/1874
|accessdate=2017-01-08 }}</ref>
 
== Structure ==
 
The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a [[DNA binding domain]], a [[protein dimer|dimerization]] domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a [[transactivation]] domain enriched in acidic amino acids ([[aspartic acid|Asp]] + [[glutamic acid|Glu]]), and a tumor suppressor protein association domain which is embedded within the transactivation domain.
 
==Interactions==
E2F4 has been shown to [[Protein-protein interaction|interact]] with [[Smad3]].<ref name="pmid12150994">{{cite journal | vauthors = Chen CR, Kang Y, Siegel PM, Massagué J | title = E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression | journal = Cell | volume = 110 | issue = 1 | pages = 19–32 |date=July 2002 | pmid = 12150994 | doi = 10.1016/S0092-8674(02)00801-2 }}</ref>
 
== Clinical significance ==
 
=== Colorectal cancers ===
 
"The AGC triplet repeat in the coding region of the E2F-4 gene, a member of the family, has been reported to be mutated in colorectal cancers with a microsatellite instability (MSI) phenotype. We found a wider range variation of the repeat number in DNAs from tumors, the corresponding normal mucosa, and healthy individuals. A total of 5 repeat variants, ranging from 8 to 17 AGC repeats, was detected in 6 (9.7%) of the 62 healthy individuals and 8 (8.9%) of the 90 normal DNAs of the patients. The wild-type 13 repeat was present in all of these individuals. The variation of the AGC repeat number may be a polymorphism. Further, loss of heterozygosity (LOH) at the E2F-4 locus in the tumor tissues of 2 (25%) of the 8 informative cases was detected."<ref name=Zhong>{{ cite journal
|author=X. Zhong, H. Hemmi, J. Koike, K. Tsujita, H. Shimatake
|title=Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4
|journal=Human Mutation
|date=March 2000
|volume=15
|issue=3
|pages=296-7
|url=https://www.ncbi.nlm.nih.gov/pubmed/10679953
|arxiv=
|bibcode=
|doi=10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU18>3.0.CO;2-X
|pmid=10679953
|accessdate=2017-01-08 }}</ref>


==See also==
==See also==
Line 59: Line 44:


==References==
==References==
{{reflist|2}}
{{reflist}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  | vauthors=Bandyopadhyay D, Timchenko N, Suwa T |title=The human melanocyte: a model system to study the complexity of cellular aging and transformation in non-fibroblastic cells. |journal=Exp. Gerontol. |volume=36 |issue= 8 |pages= 1265–75 |year= 2001 |pmid= 11602203 |doi=10.1016/S0531-5565(01)00098-5 |display-authors=etal}}
| citations =
*{{cite journal  | vauthors=Beijersbergen RL, Kerkhoven RM, Zhu L |title=E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. |journal=Genes Dev. |volume=8 |issue= 22 |pages= 2680–90 |year= 1994 |pmid= 7958925 |doi=10.1101/gad.8.22.2680 |display-authors=etal}}
*{{cite journal  | author=Bandyopadhyay D, Timchenko N, Suwa T, ''et al.'' |title=The human melanocyte: a model system to study the complexity of cellular aging and transformation in non-fibroblastic cells. |journal=Exp. Gerontol. |volume=36 |issue= 8 |pages= 1265-75 |year= 2001 |pmid= 11602203 |doi=  }}
*{{cite journal  | vauthors=Xiao ZX, Ginsberg D, Ewen M, Livingston DM |title=Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 10 |pages= 4633–7 |year= 1996 |pmid= 8643455 |doi=10.1073/pnas.93.10.4633  | pmc=39330  }}
*{{cite journal  | author=Sardet C, Vidal M, Cobrinik D, ''et al.'' |title=E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 6 |pages= 2403-7 |year= 1995 |pmid= 7892279 |doi=  }}
*{{cite journal  | vauthors=Moberg K, Starz MA, Lees JA |title=E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. |journal=Mol. Cell. Biol. |volume=16 |issue= 4 |pages= 1436–49 |year= 1996 |pmid= 8657117 |doi= | pmc=231128 }}
*{{cite journal  | author=Ginsberg D, Vairo G, Chittenden T, ''et al.'' |title=E2F-4, a new member of the E2F transcription factor family, interacts with p107. |journal=Genes Dev. |volume=8 |issue= 22 |pages= 2665-79 |year= 1994 |pmid= 7958924 |doi= }}
*{{cite journal  | vauthors=Vidal M, Brachmann RK, Fattaey A |title=Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 19 |pages= 10315–20 |year= 1996 |pmid= 8816797 |doi=10.1073/pnas.93.19.10315 | pmc=38381  |display-authors=etal}}
*{{cite journal  | author=Beijersbergen RL, Kerkhoven RM, Zhu L, ''et al.'' |title=E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. |journal=Genes Dev. |volume=8 |issue= 22 |pages= 2680-90 |year= 1994 |pmid= 7958925 |doi=  }}
*{{cite journal  | vauthors=Williams CD, Linch DC, Sørensen TS |title=The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130. |journal=Br. J. Haematol. |volume=96 |issue= 4 |pages= 688–96 |year= 1997 |pmid= 9074408 |doi=10.1046/j.1365-2141.1997.d01-2086.x |display-authors=etal}}
*{{cite journal  | author=Xiao ZX, Ginsberg D, Ewen M, Livingston DM |title=Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 10 |pages= 4633-7 |year= 1996 |pmid= 8643455 |doi=  }}
*{{cite journal  | vauthors=Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D |title=The subcellular localization of E2F-4 is cell-cycle dependent. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 10 |pages= 5095–100 |year= 1997 |pmid= 9144196 |doi=10.1073/pnas.94.10.5095  | pmc=24637  }}
*{{cite journal  | author=Moberg K, Starz MA, Lees JA |title=E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. |journal=Mol. Cell. Biol. |volume=16 |issue= 4 |pages= 1436-49 |year= 1996 |pmid= 8657117 |doi=  }}
*{{cite journal  | vauthors=Wang H, Shao N, Ding QM |title=BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases. |journal=Oncogene |volume=15 |issue= 2 |pages= 143–57 |year= 1997 |pmid= 9244350 |doi= 10.1038/sj.onc.1201252 |display-authors=etal}}
*{{cite journal  | author=Vidal M, Brachmann RK, Fattaey A, ''et al.'' |title=Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 19 |pages= 10315-20 |year= 1996 |pmid= 8816797 |doi= }}
*{{cite journal  | vauthors=Müller H, Moroni MC, Vigo E |title=Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. |journal=Mol. Cell. Biol. |volume=17 |issue= 9 |pages= 5508–20 |year= 1997 |pmid= 9271426 |doi=  | pmc=232399  |display-authors=etal}}
*{{cite journal  | author=Williams CD, Linch DC, Sørensen TS, ''et al.'' |title=The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130. |journal=Br. J. Haematol. |volume=96 |issue= 4 |pages= 688-96 |year= 1997 |pmid= 9074408 |doi= }}
*{{cite journal  | vauthors=Pierce AM, Schneider-Broussard R, Philhower JL, Johnson DG |title=Differential activities of E2F family members: unique functions in regulating transcription. |journal=Mol. Carcinog. |volume=22 |issue= 3 |pages= 190–8 |year= 1998 |pmid= 9688145 |doi=10.1002/(SICI)1098-2744(199807)22:3<190::AID-MC7>3.0.CO;2-P  }}
*{{cite journal  | author=Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D |title=The subcellular localization of E2F-4 is cell-cycle dependent. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 10 |pages= 5095-100 |year= 1997 |pmid= 9144196 |doi=  }}
*{{cite journal  | vauthors=Ferreira R, Magnaghi-Jaulin L, Robin P |title=The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 18 |pages= 10493–8 |year= 1998 |pmid= 9724731 |doi=10.1073/pnas.95.18.10493 | pmc=27922  |display-authors=etal}}
*{{cite journal  | author=Wang H, Shao N, Ding QM, ''et al.'' |title=BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases. |journal=Oncogene |volume=15 |issue= 2 |pages= 143-57 |year= 1997 |pmid= 9244350 |doi= 10.1038/sj.onc.1201252 }}
*{{cite journal  | vauthors=Timchenko NA, Wilde M, Darlington GJ |title=C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. |journal=Mol. Cell. Biol. |volume=19 |issue= 4 |pages= 2936–45 |year= 1999 |pmid= 10082561 |doi= | pmc=84088 }}
*{{cite journal  | author=Müller H, Moroni MC, Vigo E, ''et al.'' |title=Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. |journal=Mol. Cell. Biol. |volume=17 |issue= 9 |pages= 5508-20 |year= 1997 |pmid= 9271426 |doi=  }}
*{{cite journal  | vauthors=Zheng N, Fraenkel E, Pabo CO, Pavletich NP |title=Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP. |journal=Genes Dev. |volume=13 |issue= 6 |pages= 666–74 |year= 1999 |pmid= 10090723 |doi=10.1101/gad.13.6.666  | pmc=316551 }}
*{{cite journal  | author=Pierce AM, Schneider-Broussard R, Philhower JL, Johnson DG |title=Differential activities of E2F family members: unique functions in regulating transcription. |journal=Mol. Carcinog. |volume=22 |issue= 3 |pages= 190-8 |year= 1998 |pmid= 9688145 |doi=  }}
*{{cite journal  | vauthors=Furukawa Y, Iwase S, Kikuchi J |title=Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes. |journal=Oncogene |volume=18 |issue= 11 |pages= 2003–14 |year= 1999 |pmid= 10208422 |doi= 10.1038/sj.onc.1202500 |display-authors=etal}}
*{{cite journal  | author=Ferreira R, Magnaghi-Jaulin L, Robin P, ''et al.'' |title=The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 18 |pages= 10493-8 |year= 1998 |pmid= 9724731 |doi=  }}
*{{cite journal  | vauthors=Lam EW, Glassford J, van der Sman J |title=Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors. |journal=Eur. J. Immunol. |volume=29 |issue= 10 |pages= 3380–9 |year= 1999 |pmid= 10540350 |doi=10.1002/(SICI)1521-4141(199910)29:10<3380::AID-IMMU3380>3.0.CO;2-C  |display-authors=etal}}
*{{cite journal  | author=Timchenko NA, Wilde M, Darlington GJ |title=C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. |journal=Mol. Cell. Biol. |volume=19 |issue= 4 |pages= 2936-45 |year= 1999 |pmid= 10082561 |doi= }}
*{{cite journal  | vauthors=Zhong X, Hemmi H, Koike J |title=Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4. |journal=Hum. Mutat. |volume=15 |issue= 3 |pages= 296–7 |year= 2000 |pmid= 10679953 |doi= 10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU18>3.0.CO;2-X |display-authors=etal}}
*{{cite journal  | author=Zheng N, Fraenkel E, Pabo CO, Pavletich NP |title=Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP. |journal=Genes Dev. |volume=13 |issue= 6 |pages= 666-74 |year= 1999 |pmid= 10090723 |doi= }}
*{{cite journal  | vauthors=Takahashi Y, Rayman JB, Dynlacht BD |title=Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. |journal=Genes Dev. |volume=14 |issue= 7 |pages= 804–16 |year= 2000 |pmid= 10766737 |doi= 10.1101/gad.14.7.804| pmc=316494 }}
*{{cite journal  | author=Furukawa Y, Iwase S, Kikuchi J, ''et al.'' |title=Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes. |journal=Oncogene |volume=18 |issue= 11 |pages= 2003-14 |year= 1999 |pmid= 10208422 |doi= 10.1038/sj.onc.1202500 }}
*{{cite journal  | vauthors=Schwemmle S, Pfeifer GP |title=Genomic structure and mutation screening of the E2F4 gene in human tumors. |journal=Int. J. Cancer |volume=86 |issue= 5 |pages= 672–7 |year= 2000 |pmid= 10797289 |doi=10.1002/(SICI)1097-0215(20000601)86:5<672::AID-IJC11>3.0.CO;2-X  }}
*{{cite journal  | author=Lam EW, Glassford J, van der Sman J, ''et al.'' |title=Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors. |journal=Eur. J. Immunol. |volume=29 |issue= 10 |pages= 3380-9 |year= 1999 |pmid= 10540350 |doi=  }}
*{{cite journal  | author=Zhong X, Hemmi H, Koike J, ''et al.'' |title=Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4. |journal=Hum. Mutat. |volume=15 |issue= 3 |pages= 296-7 |year= 2000 |pmid= 10679953 |doi= 10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU18>3.0.CO;2-X }}
*{{cite journal | author=Takahashi Y, Rayman JB, Dynlacht BD |title=Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. |journal=Genes Dev. |volume=14 |issue= 7 |pages= 804-16 |year= 2000 |pmid= 10766737 |doi=  }}
*{{cite journal  | author=Schwemmle S, Pfeifer GP |title=Genomic structure and mutation screening of the E2F4 gene in human tumors. |journal=Int. J. Cancer |volume=86 |issue= 5 |pages= 672-7 |year= 2000 |pmid= 10797289 |doi=  }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|E2F4+protein,+human}}
* {{MeshName|E2F4+protein,+human}}
* {{FactorBook|E2F4}}


{{NLM content}}
{{NLM content}}
{{PDB Gallery|geneid=1874}}
{{Transcription factors|g3}}
[[Category:Transcription factors]]
{{gene-16-stub}}
{{gene-16-stub}}
{{Transcription factors}}
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Latest revision as of 03:36, 20 November 2019

Associate Editor(s)-in-Chief: Henry A. Hoff

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

n/a

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UniProt

n/a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Transcription factor E2F4 is a protein that in humans is encoded by the E2F4 gene.[1][2]

Function

Gene ID: 1874 E2F transcription factor 4, "The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer."[3]

Structure

The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids (Asp + Glu), and a tumor suppressor protein association domain which is embedded within the transactivation domain.

Interactions

E2F4 has been shown to interact with Smad3.[4]

Clinical significance

Colorectal cancers

"The AGC triplet repeat in the coding region of the E2F-4 gene, a member of the family, has been reported to be mutated in colorectal cancers with a microsatellite instability (MSI) phenotype. We found a wider range variation of the repeat number in DNAs from tumors, the corresponding normal mucosa, and healthy individuals. A total of 5 repeat variants, ranging from 8 to 17 AGC repeats, was detected in 6 (9.7%) of the 62 healthy individuals and 8 (8.9%) of the 90 normal DNAs of the patients. The wild-type 13 repeat was present in all of these individuals. The variation of the AGC repeat number may be a polymorphism. Further, loss of heterozygosity (LOH) at the E2F-4 locus in the tumor tissues of 2 (25%) of the 8 informative cases was detected."[5]

See also

References

  1. ↑ Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM (Dec 1994). "E2F-4, a new member of the E2F transcription factor family, interacts with p107". Genes Dev. 8 (22): 2665–79. doi:10.1101/gad.8.22.2665. PMID 7958924.
  2. ↑ Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA (Apr 1995). "E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle". Proc Natl Acad Sci U S A. 92 (6): 2403–7. doi:10.1073/pnas.92.6.2403. PMC 42492. PMID 7892279.
  3. ↑ RefSeqJuly2008 (25 December 2016). "E2F4 E2F transcription factor 4 [ Homo sapiens (human) ]". U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information. Retrieved 2017-01-08.
  4. ↑ Chen CR, Kang Y, Siegel PM, Massagué J (July 2002). "E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression". Cell. 110 (1): 19–32. doi:10.1016/S0092-8674(02)00801-2. PMID 12150994.
  5. ↑ X. Zhong, H. Hemmi, J. Koike, K. Tsujita, H. Shimatake (March 2000). "Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4". Human Mutation. 15 (3): 296–7. doi:10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU18>3.0.CO;2-X. PMID 10679953. Retrieved 2017-01-08.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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