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{{Redirect|CRP2|the airport|Reston/R.M. of Pipestone Airport}}
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{{Infobox_gene}}
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'''CCAAT/enhancer-binding protein beta''' is a [[protein]] that in humans is encoded by the ''CEBPB'' [[gene]].<ref name="pmid1535333">{{cite journal | vauthors = Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J | title = Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF) | journal = Genomics | volume = 13 | issue = 2 | pages = 293–300 | date = Jul 1992 | pmid = 1535333 | pmc =  | doi = 10.1016/0888-7543(92)90245-N }}</ref><ref name="pmid1840554">{{cite journal | vauthors = Cao Z, Umek RM, McKnight SL | title = Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells | journal = Genes Dev | volume = 5 | issue = 9 | pages = 1538–52 | date = Oct 1991 | pmid = 1840554 | pmc = | doi = 10.1101/gad.5.9.1538 }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
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<!-- 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_CEBPB_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ci6.
| PDB = {{PDB2|1ci6}}, {{PDB2|1gtw}}, {{PDB2|1gu4}}, {{PDB2|1gu5}}, {{PDB2|1h88}}, {{PDB2|1h89}}, {{PDB2|1h8a}}, {{PDB2|1hjb}}, {{PDB2|1io4}}
| Name = CCAAT/enhancer binding protein (C/EBP), beta
| HGNCid = 1834
| Symbol = CEBPB
| AltSymbols =; C/EBP-beta; CRP2; IL6DBP; LAP; MGC32080; NF-IL6; TCF5
| OMIM = 189965
| ECnumber = 
| Homologene = 3807
| MGIid = 88373
| GeneAtlas_image1 = PBB_GE_CEBPB_212501_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0016563 |text = transcription activator activity}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}} {{GNF_GO|id=GO:0046982 |text = protein heterodimerization activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0001892 |text = embryonic placenta development}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0006366 |text = transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006916 |text = anti-apoptosis}} {{GNF_GO|id=GO:0006917 |text = induction of apoptosis}} {{GNF_GO|id=GO:0006953 |text = acute-phase response}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0030182 |text = neuron differentiation}} {{GNF_GO|id=GO:0045408 |text = regulation of interleukin-6 biosynthetic process}} {{GNF_GO|id=GO:0045444 |text = fat cell differentiation}} {{GNF_GO|id=GO:0045941 |text = positive regulation of transcription}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1051
    | Hs_Ensembl = ENSG00000172216
    | Hs_RefseqProtein = NP_005185
    | Hs_RefseqmRNA = NM_005194
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 48240678
    | Hs_GenLoc_end = 48242633
    | Hs_Uniprot = P17676
    | Mm_EntrezGene = 12608
    | Mm_Ensembl = ENSMUSG00000056501
    | Mm_RefseqmRNA = NM_009883
    | Mm_RefseqProtein = NP_034013
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 167380120
    | Mm_GenLoc_end = 167381623
    | Mm_Uniprot = Q3UPN9
  }}
}}
'''CCAAT/enhancer binding protein (C/EBP), beta''', also known as '''CEBPB''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this intronless gene is a [[BZIP domain|bZIP]] transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins [[CEBPA|CEBP-alpha]], [[CEBPD|CEBP-delta]], and [[CEBPG|CEBP-gamma]]. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the [[Interleukin 1|IL-1]] response element in the [[Interleukin 6|IL-6]] gene, as well as to regulatory regions of several acute-phase and [[cytokine]] genes. In addition, the encoded protein can bind the promoter and upstream element and stimulate the expression of the [[type-I collagen|collagen type I]] gene.<ref>{{cite web | title = Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1051| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this intronless gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, the encoded protein can bind the promoter and upstream element and stimulate the expression of the collagen type I gene.<ref>{{cite web | title = Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1051| accessdate = }}</ref>
}}


==See also==
CEBP-beta is critical for normal [[macrophage]] functioning, an important [[Immune system|immune]] cell [[Leukocyte|sub-type]]; [[Mouse|mice]] unable to [[Gene expression|express]] CEBP-beta have macrophages that cannot [[Cellular differentiation|differentiate]] (specialize) and thus are unable to perform all their biological functions - including macrophage-mediated muscle repair.<ref name=ruffel_mice>{{cite journal | vauthors = Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG, Rosenthal N, Nerlov C | title = A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 41 | pages = 17475–80 | year = 2009 | pmid = 19805133 | pmc = 2762675 | doi = 10.1073/pnas.0908641106 }}</ref> [[Epidemiology|Observational]] work has shown that [[gene expression|expression]] of CEBP-beta in blood [[leukocyte]]s is positively associated with muscle strength in [[Homo sapiens|humans]],<ref name=harries_cebpb>{{cite journal | vauthors = Harries LW, Pilling LC, Hernandez LD, Bradley-Smith R, Henley W, Singleton AB, Guralnik JM, Bandinelli S, Ferrucci L, Melzer D | title = CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength | journal = Aging Cell | volume = 11 | issue = 2 | pages = 262–8 | year = 2012 | pmid = 22152057 | pmc = 3486692 | doi = 10.1111/j.1474-9726.2011.00782.x }}</ref> emphasizing the importance of the immune system, and particularly macrophages, in the maintenance of muscle function.
 
Function of CEBPB gene can be effectively examined by siRNA knockdown based on an independent validation.<ref>{{Cite journal|last=Munkácsy|first=Gyöngyi|last2=Sztupinszki|first2=Zsófia|last3=Herman|first3=Péter|last4=Bán|first4=Bence|last5=Pénzváltó|first5=Zsófia|last6=Szarvas|first6=Nóra|last7=Győrffy|first7=Balázs|date=2016-01-01|title=Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments|url=http://linkinghub.elsevier.com/retrieve/pii/S2162253117300859|journal=Molecular Therapy - Nucleic Acids|language=English|volume=5|issue=9|pages=e366|doi=10.1038/mtna.2016.66|issn=2162-2531|pmc=5056990|pmid=27673562}}</ref>
 
== Target genes ==
 
CEBPB is capable of increasing the expression of several target genes.  Among them, some have specific role in the nervous system such as the [[preprotachykinin-1]] gene, giving rise to [[substance P]] and [[neurokinin A]]<ref name="pmid16771829">{{cite journal | vauthors = Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR | title = C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones | journal = J. Neurochem. | volume = 98 | issue = 5 | pages = 1390–9 | date = September 2006 | pmid = 16771829 | doi = 10.1111/j.1471-4159.2006.03957.x }}</ref> and the [[choline acetyltransferase]] responsible for the biosynthesis of the important [[neurotransmitter]] [[acetylcholine]].<ref name="pmid12393272">{{cite journal | vauthors = Robert I, Sutter A, Quirin-Stricker C | title = Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta | journal = Brain Res. Mol. Brain Res. | volume = 106 | issue = 1–2 | pages = 124–35 | date = October 2002 | pmid = 12393272 | doi = 10.1016/S0169-328X(02)00419-9 }}</ref>
Other targets include genes coding for cytokines such as [[interleukin 6|IL-6]],<ref name="pmid1730090">{{cite journal | vauthors = Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H, Kishimoto T | title = Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6 | journal = Blood | volume = 79 | issue = 2 | pages = 460–6 | date = January 1992 | pmid = 1730090 | doi =  }}</ref> [[interleukin 4|IL-4]],<ref name="pmid7594540">{{cite journal | vauthors = Davydov IV, Krammer PH, Li-Weber M | title = Nuclear factor-IL6 activates the human IL-4 promoter in T cells | journal = J. Immunol. | volume = 155 | issue = 11 | pages = 5273–9 | date = December 1995 | pmid = 7594540 | doi =  }}</ref> [[interleukin 5|IL-5]],<ref name="pmid10453008">{{cite journal | vauthors = van Dijk TB, Baltus B, Raaijmakers JA, Lammers JW, Koenderman L, de Groot RP | title = A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene | journal = J. Immunol. | volume = 163 | issue = 5 | pages = 2674–80 | date = September 1999 | pmid = 10453008 }}</ref> and [[tumor necrosis factor-alpha|TNF-alpha]].<ref name="pmid10629048">{{cite journal | vauthors = Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F | title = Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins | journal = Mol. Cell. Biol. | volume = 20 | issue = 3 | pages = 912–8 | date = February 2000 | pmid = 10629048 | pmc = 85208 | doi = 10.1128/MCB.20.3.912-918.2000 }}</ref>
Genes coding for transporter proteins that confer multidrug resistance to the cells have also been found to be activated by CEBPB. Such genes include [[multidrug resistance-associated protein 2|ABCC2]]<ref name="pmid10573531">{{cite journal | vauthors = Tanaka T, Uchiumi T, Hinoshita E, Inokuchi A, Toh S, Wada M, Takano H, Kohno K, Kuwano M | title = The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells | journal = Hepatology | volume = 30 | issue = 6 | pages = 1507–12 | date = December 1999 | pmid = 10573531 | doi = 10.1002/hep.510300617 }}</ref> and [[p-glycoprotein|ABCB1]].<ref name="pmid15044620">{{cite journal | vauthors = Chen GK, Sale S, Tan T, Ermoian RP, Sikic BI | title = CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells | journal = Mol. Pharmacol. | volume = 65 | issue = 4 | pages = 906–16 | date = April 2004 | pmid = 15044620 | doi = 10.1124/mol.65.4.906 }}</ref>
 
== Interactions ==
 
CEBPB has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[CREB1]],<ref name = pmid12773552>{{cite journal | vauthors = Chen Y, Zhuang S, Cassenaer S, Casteel DE, Gudi T, Boss GR, Pilz RB | title = Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires cooperation between CREB and C/EBP-beta | journal = Mol. Cell. Biol. | volume = 23 | issue = 12 | pages = 4066–82 | pmid = 12773552 | pmc = 156132 | doi = 10.1128/mcb.23.12.4066-4082.2003 | year = 2003 }}</ref>
* [[CRSP3]]<ref name = pmid14759369>{{cite journal | vauthors = Mo X, Kowenz-Leutz E, Xu H, Leutz A | title = Ras induces mediator complex exchange on C/EBP beta | journal = Mol. Cell | volume = 13 | issue = 2 | pages = 241–50 | pmid = 14759369 | doi = 10.1016/s1097-2765(03)00521-5 | date=January 2004}}</ref>
* [[DNA damage-inducible transcript 3]],<ref name = pmid12706815>{{cite journal | vauthors = Hattori T, Ohoka N, Hayashi H, Onozaki K | title = C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform | journal = FEBS Lett. | volume = 541 | issue = 1–3 | pages = 33–9 | pmid = 12706815 | doi = 10.1016/s0014-5793(03)00283-7 | date=April 2003}}</ref><ref name = pmid8662954>{{cite journal | vauthors = Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ | title = Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress | journal = J. Biol. Chem. | volume = 271 | issue = 24 | pages = 14285–9 | pmid = 8662954 | doi = 10.1074/jbc.271.24.14285 | date=June 1996}}</ref>
* [[EP300]],<ref name = pmid9343424>{{cite journal | vauthors = Mink S, Haenig B, Klempnauer KH | title = Interaction and functional collaboration of p300 and C/EBPbeta | journal = Mol. Cell. Biol. | volume = 17 | issue = 11 | pages = 6609–17 | date = November 1997 | pmid = 9343424 | pmc = 232514 | doi =  10.1128/mcb.17.11.6609}}</ref>
* [[Estrogen receptor alpha]],<ref name = pmid9817600/><ref name = pmid7651415>{{cite journal | vauthors = Stein B, Yang MX | title = Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta | journal = Mol. Cell. Biol. | volume = 15 | issue = 9 | pages = 4971–9 | date = September 1995 | pmid = 7651415 | pmc = 230744 | doi =  }}</ref>
* [[Glucocorticoid receptor]],<ref name = pmid9817600>{{cite journal | vauthors = Boruk M, Savory JG, Haché RJ | title = AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor | journal = Mol. Endocrinol. | volume = 12 | issue = 11 | pages = 1749–63 | pmid = 9817600 | doi = 10.1210/mend.12.11.0191 | date=November 1998}}</ref>
* [[HMGA1]],<ref name = pmid12665574/>
* [[HSF1]],<ref name = pmid11801594>{{cite journal | vauthors = Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK | title = Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6 | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 11802–10 | pmid = 11801594 | doi = 10.1074/jbc.M109296200 | date=April 2002}}</ref>
* [[Nucleolar phosphoprotein p130]],<ref name = pmid9553145>{{cite journal | vauthors = Miau LH, Chang CJ, Shen BJ, Tsai WH, Lee SC | title = Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation | journal = J. Biol. Chem. | volume = 273 | issue = 17 | pages = 10784–91 | pmid = 9553145 | doi = 10.1074/jbc.273.17.10784 | date=April 1998}}</ref>
* [[RELA]],<ref name = pmid12707271>{{cite journal | vauthors = Weber M, Sydlik C, Quirling M, Nothdurfter C, Zwergal A, Heiss P, Bell S, Neumeier D, Ziegler-Heitbrock HW, Brand K | title = Transcriptional inhibition of interleukin-8 expression in tumor necrosis factor-tolerant cells: evidence for involvement of C/EBP beta | journal = J. Biol. Chem. | volume = 278 | issue = 26 | pages = 23586–93 | pmid = 12707271 | doi = 10.1074/jbc.M211646200 | date=June 2003}}</ref><ref name = pmid9570146>{{cite journal | vauthors = Xia C, Cheshire JK, Patel H, Woo P | title = Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes | journal = Int. J. Biochem. Cell Biol. | volume = 29 | issue = 12 | pages = 1525–39 | pmid = 9570146 | doi = 10.1016/s1357-2725(97)00083-6 | date=December 1997}}</ref>
* [[Serum response factor]],<ref name = pmid10318842>{{cite journal | vauthors = Hanlon M, Sealy L | title = Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta | journal = J. Biol. Chem. | volume = 274 | issue = 20 | pages = 14224–8 | pmid = 10318842 | doi = 10.1074/jbc.274.20.14224 | date=May 1999}}</ref><ref name = pmid9032301>{{cite journal | vauthors = Sealy L, Malone D, Pawlak M | title = Regulation of the cfos serum response element by C/EBPbeta | journal = Mol. Cell. Biol. | volume = 17 | issue = 3 | pages = 1744–55 | date = March 1997 | pmid = 9032301 | pmc = 231899 | doi =  10.1128/mcb.17.3.1744}}</ref>
* [[SMARCA2]],<ref name = pmid10619021>{{cite journal | vauthors = Kowenz-Leutz E, Leutz A | title = A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes | journal = Mol. Cell | volume = 4 | issue = 5 | pages = 735–43 | pmid = 10619021 | doi = 10.1016/s1097-2765(00)80384-6 | date=November 1999}}</ref>
* [[Sp1 transcription factor]],<ref name = pmid12665574>{{cite journal | vauthors = Foti D, Iuliano R, Chiefari E, Brunetti A | title = A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription | journal = Mol. Cell. Biol. | volume = 23 | issue = 8 | pages = 2720–32 | pmid = 12665574 | pmc = 152545 | doi = 10.1128/mcb.23.8.2720-2732.2003 | year = 2003 }}</ref><ref name = pmid12847250>{{cite journal | vauthors = Liu YW, Tseng HP, Chen LC, Chen BK, Chang WC | title = Functional cooperation of simian virus 40 promoter factor 1 and CCAAT/enhancer-binding protein beta and delta in lipopolysaccharide-induced gene activation of IL-10 in mouse macrophages | journal = J. Immunol. | volume = 171 | issue = 2 | pages = 821–8 | pmid = 12847250 | doi = 10.4049/jimmunol.171.2.821 | date=July 2003}}</ref>
* [[TRIM28]],<ref name = pmid11711437>{{cite journal | vauthors = Rooney JW, Calame KL | title = TIF1beta functions as a coactivator for C/EBPbeta and is required for induced differentiation in the myelomonocytic cell line U937 | journal = Genes Dev. | volume = 15 | issue = 22 | pages = 3023–38 | pmid = 11711437 | pmc = 312827 | doi = 10.1101/gad.937201 | year = 2001 }}</ref><ref name = pmid9742105>{{cite journal | vauthors = Chang CJ, Chen YL, Lee SC | title = Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression | journal = Mol. Cell. Biol. | volume = 18 | issue = 10 | pages = 5880–7 | date = October 1998 | pmid = 9742105 | pmc = 109174 | doi =  10.1128/mcb.18.10.5880}}</ref>  and
* [[Zif268]].<ref name = pmid12947119>{{cite journal | vauthors = Zhang F, Lin M, Abidi P, Thiel G, Liu J | title = Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene | journal = J. Biol. Chem. | volume = 278 | issue = 45 | pages = 44246–54 | pmid = 12947119 | doi = 10.1074/jbc.M305564200 | date=November 2003}}</ref>
{{Div col end}}
 
== See also ==
* [[Ccaat-enhancer-binding proteins]]
* [[Ccaat-enhancer-binding proteins]]
{{Clear}}


==References==
== References ==
{{reflist|2}}
{{reflist|colwidth=35em}}
 
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Sladek FM, Darnell JE |title=Mechanisms of liver-specific gene expression. |journal=Curr. Opin. Genet. Dev. |volume=2 |issue= 2 |pages= 256-9 |year= 1992 |pmid= 1638120 |doi=  }}
*{{cite journal  | author=Maytin EV, Habener JF |title=Transcription factors C/EBP alpha, C/EBP beta, and CHOP (Gadd153) expressed during the differentiation program of keratinocytes in vitro and in vivo. |journal=J. Invest. Dermatol. |volume=110 |issue= 3 |pages= 238-46 |year= 1998 |pmid= 9506442 |doi= 10.1046/j.1523-1747.1998.00123.x }}
*{{cite journal  | author=Cornwall GA, Hsia N |title=[Cres (cystatin-related epididymal spermatogenic) gene regulation and function] |journal=Zhonghua Nan Ke Xue |volume=8 |issue= 5 |pages= 313-8 |year= 2003 |pmid= 12479114 |doi=  }}
}}
{{refend}}


== External links ==
== External links ==
* {{UCSC gene info|CEBPB}}
* {{MeshName|CEBPB+protein,+human}}
* {{MeshName|CEBPB+protein,+human}}
* {{FactorBook|CEBPB}}
{{NLM content}}
{{PDB Gallery|geneid=1051}}
{{Transcription factors|g1}}


{{NLM content}}
{{gene-20-stub}}
{{Transcription factors}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Latest revision as of 09:31, 30 August 2017

"CRP2" redirects here. For the airport, see Reston/R.M. of Pipestone Airport.
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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View/Edit Human

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.[1][2]

Function

The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, the encoded protein can bind the promoter and upstream element and stimulate the expression of the collagen type I gene.[3]

CEBP-beta is critical for normal macrophage functioning, an important immune cell sub-type; mice unable to express CEBP-beta have macrophages that cannot differentiate (specialize) and thus are unable to perform all their biological functions - including macrophage-mediated muscle repair.[4] Observational work has shown that expression of CEBP-beta in blood leukocytes is positively associated with muscle strength in humans,[5] emphasizing the importance of the immune system, and particularly macrophages, in the maintenance of muscle function.

Function of CEBPB gene can be effectively examined by siRNA knockdown based on an independent validation.[6]

Target genes

CEBPB is capable of increasing the expression of several target genes. Among them, some have specific role in the nervous system such as the preprotachykinin-1 gene, giving rise to substance P and neurokinin A[7] and the choline acetyltransferase responsible for the biosynthesis of the important neurotransmitter acetylcholine.[8] Other targets include genes coding for cytokines such as IL-6,[9] IL-4,[10] IL-5,[11] and TNF-alpha.[12] Genes coding for transporter proteins that confer multidrug resistance to the cells have also been found to be activated by CEBPB. Such genes include ABCC2[13] and ABCB1.[14]

Interactions

CEBPB has been shown to interact with:

See also

References

  1. ↑ Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (Jul 1992). "Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF)". Genomics. 13 (2): 293–300. doi:10.1016/0888-7543(92)90245-N. PMID 1535333.
  2. ↑ Cao Z, Umek RM, McKnight SL (Oct 1991). "Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells". Genes Dev. 5 (9): 1538–52. doi:10.1101/gad.5.9.1538. PMID 1840554.
  3. ↑ "Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta".
  4. ↑ Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG, Rosenthal N, Nerlov C (2009). "A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair". Proc. Natl. Acad. Sci. U.S.A. 106 (41): 17475–80. doi:10.1073/pnas.0908641106. PMC 2762675. PMID 19805133.
  5. ↑ Harries LW, Pilling LC, Hernandez LD, Bradley-Smith R, Henley W, Singleton AB, Guralnik JM, Bandinelli S, Ferrucci L, Melzer D (2012). "CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength". Aging Cell. 11 (2): 262–8. doi:10.1111/j.1474-9726.2011.00782.x. PMC 3486692. PMID 22152057.
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  7. ↑ Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR (September 2006). "C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones". J. Neurochem. 98 (5): 1390–9. doi:10.1111/j.1471-4159.2006.03957.x. PMID 16771829.
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  12. ↑ Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F (February 2000). "Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins". Mol. Cell. Biol. 20 (3): 912–8. doi:10.1128/MCB.20.3.912-918.2000. PMC 85208. PMID 10629048.
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  16. ↑ Mo X, Kowenz-Leutz E, Xu H, Leutz A (January 2004). "Ras induces mediator complex exchange on C/EBP beta". Mol. Cell. 13 (2): 241–50. doi:10.1016/s1097-2765(03)00521-5. PMID 14759369.
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  20. ↑ 20.0 20.1 Boruk M, Savory JG, Haché RJ (November 1998). "AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor". Mol. Endocrinol. 12 (11): 1749–63. doi:10.1210/mend.12.11.0191. PMID 9817600.
  21. ↑ Stein B, Yang MX (September 1995). "Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta". Mol. Cell. Biol. 15 (9): 4971–9. PMC 230744. PMID 7651415.
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  23. ↑ Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK (April 2002). "Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6". J. Biol. Chem. 277 (14): 11802–10. doi:10.1074/jbc.M109296200. PMID 11801594.
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  25. ↑ Weber M, Sydlik C, Quirling M, Nothdurfter C, Zwergal A, Heiss P, Bell S, Neumeier D, Ziegler-Heitbrock HW, Brand K (June 2003). "Transcriptional inhibition of interleukin-8 expression in tumor necrosis factor-tolerant cells: evidence for involvement of C/EBP beta". J. Biol. Chem. 278 (26): 23586–93. doi:10.1074/jbc.M211646200. PMID 12707271.
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  31. ↑ Rooney JW, Calame KL (2001). "TIF1beta functions as a coactivator for C/EBPbeta and is required for induced differentiation in the myelomonocytic cell line U937". Genes Dev. 15 (22): 3023–38. doi:10.1101/gad.937201. PMC 312827. PMID 11711437.
  32. ↑ Chang CJ, Chen YL, Lee SC (October 1998). "Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression". Mol. Cell. Biol. 18 (10): 5880–7. doi:10.1128/mcb.18.10.5880. PMC 109174. PMID 9742105.
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