CEBPB

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.{{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}}

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.{{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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 41 | pages = 17475–17480 | date = October 2009 | pmid = 19805133 | pmc = 2762675 | doi = 10.1073/pnas.0908641106 | doi-access = free | bibcode = 2009PNAS..10617475R }} Observational work has shown that expression of CEBP-beta in blood leukocytes is positively associated with muscle strength in humans,{{cite journal | vauthors = Harries LW, Pilling LC, Hernandez LD, Bradley-Smith R, Henley W, Singleton AB, Guralnik JM, Bandinelli S, Ferrucci L, Melzer D | display-authors = 6 | title = CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength | journal = Aging Cell | volume = 11 | issue = 2 | pages = 262–268 | date = April 2012 | pmid = 22152057 | pmc = 3486692 | doi = 10.1111/j.1474-9726.2011.00782.x }} 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.{{cite journal | vauthors = Munkácsy G, Sztupinszki Z, Herman P, Bán B, Pénzváltó Z, Szarvas N, Győrffy B | title = Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments | journal = Molecular Therapy. Nucleic Acids | volume = 5 | issue = 9 | pages = e366 | date = September 2016 | pmid = 27673562 | pmc = 5056990 | doi = 10.1038/mtna.2016.66 }}

Upon further investigation, it was noted that CEBPB has close to 8,600 similar correlations with biological manipulations ranging from molecules to proteins or abstracted microRNAs. This protein is found in blood and is upregulated in diseases by acute myeloid leukemia, Glioma, and prostate cancer. This idea is predicated in an intracellular location and precisely localized to the nucleoplasm.

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{{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 = Journal of Neurochemistry | volume = 98 | issue = 5 | pages = 1390–1399 | date = September 2006 | pmid = 16771829 | doi = 10.1111/j.1471-4159.2006.03957.x | s2cid = 36225447 }} and the choline acetyltransferase responsible for the biosynthesis of the important neurotransmitter acetylcholine.{{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 Research. Molecular Brain Research | volume = 106 | issue = 1–2 | pages = 124–135 | date = October 2002 | pmid = 12393272 | doi = 10.1016/S0169-328X(02)00419-9 }}

Other targets include genes coding for cytokines such as IL-6,{{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 = 460–466 | date = January 1992 | pmid = 1730090 | doi = 10.1182/blood.V79.2.460.460 | doi-access = free }} IL-4,{{cite journal | vauthors = Davydov IV, Krammer PH, Li-Weber M | title = Nuclear factor-IL6 activates the human IL-4 promoter in T cells | journal = Journal of Immunology | volume = 155 | issue = 11 | pages = 5273–5279 | date = December 1995 | doi = 10.4049/jimmunol.155.11.5273 | pmid = 7594540 | s2cid = 22681826 }} IL-5,{{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 = Journal of Immunology | volume = 163 | issue = 5 | pages = 2674–2680 | date = September 1999 | doi = 10.4049/jimmunol.163.5.2674 | pmid = 10453008 | s2cid = 45357917 | doi-access = free }} and TNF-alpha.{{cite journal | vauthors = Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F | display-authors = 6 | title = Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins | journal = Molecular and Cellular Biology | volume = 20 | issue = 3 | pages = 912–918 | date = February 2000 | pmid = 10629048 | pmc = 85208 | doi = 10.1128/MCB.20.3.912-918.2000 }}

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{{cite journal | vauthors = Tanaka T, Uchiumi T, Hinoshita E, Inokuchi A, Toh S, Wada M, Takano H, Kohno K, Kuwano M | display-authors = 6 | 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 = 1507–1512 | date = December 1999 | pmid = 10573531 | doi = 10.1002/hep.510300617 | s2cid = 22514353 | doi-access = free }} and ABCB1.{{cite journal | vauthors = Chen KG, 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 = Molecular Pharmacology | volume = 65 | issue = 4 | pages = 906–916 | date = April 2004 | pmid = 15044620 | doi = 10.1124/mol.65.4.906 | s2cid = 86591291 }}

The CEBPB gene encodes a transcription factor. As previously mentioned, "It contains a leucine zipper (bZIP) domain and the encoded protein functions as a homodimer. It can also form heterodimers with enhancer-binding proteins such as alpha, delta, and gamma. The activity of this protein is important in regulating genes involving the immune and inflammatory responses, among other processes. The "AUG" start codons, resulting in multiple protein isoforms".{{Cite web |title=CEBPB protein expression summary - The Human Protein Atlas |url=https://www.proteinatlas.org/ENSG00000172216-CEBPB |access-date=2023-05-16 |website=www.proteinatlas.org}}  It was also mentioned that each of these codon has a different biological function in the body.

This pathway allows for proliferation, inhibition, and even survival. This gene is a vital part of proliferation and segregation. It's important "as the transcription factor regulates  the expression of genes that are  involved in the  immune and inflammatory response, it includes  the gluconeogenic pathway and liver recovery. It has a probiotic effect on many cell types, like hepatocytes and adipocytes. However, it exerts differential "effects on T cells by inhibiting MYC expression and promoting differentiation of the T helper lineage." It binds to the regulatory regions of several phase and cytokine genes".{{Cite web |title=Gene - CEBPB |url=https://maayanlab.cloud/Harmonizome/gene/CEBPB |access-date=2023-05-16 |website=maayanlab.cloud}}

CEBPB is a type of CEBP transcript. CEBPB{{Cite web |title=CEBPB CCAAT enhancer binding protein beta [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/1051 |access-date=2023-05-16 |website=www.ncbi.nlm.nih.gov}} gene is noted in macrophages in SKCM and provides a favorable prognosis with metastatic cancer by being a biomarker for the patient's diagnosis stratification. Through integrated analysis of single-cell and bulk RNA-sequence datasets. Since CEBPB is a transcription factor in regulating gene expression, patients with metastatic melanoma may benefit long-term by blocking proteins such as CTLA-4 Other. Any other pathway of immune activation, such as targeting CEBPB. It is widely expressed in several different cancers.

CEBPB has been shown to interact with:

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• CREB1,{{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 = Molecular and Cellular Biology | volume = 23 | issue = 12 | pages = 4066–4082 | date = June 2003 | pmid = 12773552 | pmc = 156132 | doi = 10.1128/mcb.23.12.4066-4082.2003 }}
• CRSP3{{cite journal | vauthors = Mo X, Kowenz-Leutz E, Xu H, Leutz A | title = Ras induces mediator complex exchange on C/EBP beta | journal = Molecular Cell | volume = 13 | issue = 2 | pages = 241–250 | date = January 2004 | pmid = 14759369 | doi = 10.1016/s1097-2765(03)00521-5 | doi-access = free }}
• DNA damage-inducible transcript 3,{{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 Letters | volume = 541 | issue = 1–3 | pages = 33–39 | date = April 2003 | pmid = 12706815 | doi = 10.1016/s0014-5793(03)00283-7 | s2cid = 43792576 | doi-access = free | bibcode = 2003FEBSL.541...33H }}{{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 = The Journal of Biological Chemistry | volume = 271 | issue = 24 | pages = 14285–14289 | date = June 1996 | pmid = 8662954 | doi = 10.1074/jbc.271.24.14285 | doi-access = free }}
• EP300,{{cite journal | vauthors = Mink S, Haenig B, Klempnauer KH | title = Interaction and functional collaboration of p300 and C/EBPbeta | journal = Molecular and Cellular Biology | volume = 17 | issue = 11 | pages = 6609–6617 | date = November 1997 | pmid = 9343424 | pmc = 232514 | doi = 10.1128/mcb.17.11.6609 }}
• Estrogen receptor alpha,{{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 = Molecular and Cellular Biology | volume = 15 | issue = 9 | pages = 4971–4979 | date = September 1995 | pmid = 7651415 | pmc = 230744 | doi = 10.1128/mcb.15.9.4971 }}
• Glucocorticoid receptor,{{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 = Molecular Endocrinology | volume = 12 | issue = 11 | pages = 1749–1763 | date = November 1998 | pmid = 9817600 | doi = 10.1210/mend.12.11.0191 | doi-access = free }}
• HMGA1,
• HSF1,{{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 = The Journal of Biological Chemistry | volume = 277 | issue = 14 | pages = 11802–11810 | date = April 2002 | pmid = 11801594 | doi = 10.1074/jbc.M109296200 | doi-access = free }}
• Nucleolar phosphoprotein p130,{{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 = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10784–10791 | date = April 1998 | pmid = 9553145 | doi = 10.1074/jbc.273.17.10784 | doi-access = free }}
• RELA,{{cite journal | vauthors = Weber M, Sydlik C, Quirling M, Nothdurfter C, Zwergal A, Heiss P, Bell S, Neumeier D, Ziegler-Heitbrock HW, Brand K | display-authors = 6 | title = Transcriptional inhibition of interleukin-8 expression in tumor necrosis factor-tolerant cells: evidence for involvement of C/EBP beta | journal = The Journal of Biological Chemistry | volume = 278 | issue = 26 | pages = 23586–23593 | date = June 2003 | pmid = 12707271 | doi = 10.1074/jbc.M211646200 | doi-access = free }}{{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 = The International Journal of Biochemistry & Cell Biology | volume = 29 | issue = 12 | pages = 1525–1539 | date = December 1997 | pmid = 9570146 | doi = 10.1016/s1357-2725(97)00083-6 }}
• Serum response factor,{{cite journal | vauthors = Hanlon M, Sealy L | title = Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14224–14228 | date = May 1999 | pmid = 10318842 | doi = 10.1074/jbc.274.20.14224 | doi-access = free }}{{cite journal | vauthors = Sealy L, Malone D, Pawlak M | title = Regulation of the cfos serum response element by C/EBPbeta | journal = Molecular and Cellular Biology | volume = 17 | issue = 3 | pages = 1744–1755 | date = March 1997 | pmid = 9032301 | pmc = 231899 | doi = 10.1128/mcb.17.3.1744 }}
• SMARCA2,{{cite journal | vauthors = Kowenz-Leutz E, Leutz A | title = A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes | journal = Molecular Cell | volume = 4 | issue = 5 | pages = 735–743 | date = November 1999 | pmid = 10619021 | doi = 10.1016/s1097-2765(00)80384-6 | doi-access = free }}
• Sp1 transcription factor,{{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 = Molecular and Cellular Biology | volume = 23 | issue = 8 | pages = 2720–2732 | date = April 2003 | pmid = 12665574 | pmc = 152545 | doi = 10.1128/mcb.23.8.2720-2732.2003 }}{{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 = Journal of Immunology | volume = 171 | issue = 2 | pages = 821–828 | date = July 2003 | pmid = 12847250 | doi = 10.4049/jimmunol.171.2.821 | doi-access = free }}
• TRIM28,{{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 & Development | volume = 15 | issue = 22 | pages = 3023–3038 | date = November 2001 | pmid = 11711437 | pmc = 312827 | doi = 10.1101/gad.937201 }}{{Retracted|pmc=186452|pmid=12269264|http://retractionwatch.com/2011/06/21/the-way-science-should-work-a-swift-clearly-worded-retraction-in-gd-after-legitimate-questions-by-another-group/ Retraction Watch|intentional=yes}}{{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 = Molecular and Cellular Biology | volume = 18 | issue = 10 | pages = 5880–5887 | date = October 1998 | pmid = 9742105 | pmc = 109174 | doi = 10.1128/mcb.18.10.5880 }} and
• Zif268.{{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 = The Journal of Biological Chemistry | volume = 278 | issue = 45 | pages = 44246–44254 | date = November 2003 | pmid = 12947119 | doi = 10.1074/jbc.M305564200 | doi-access = free }}

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• Ccaat-enhancer-binding proteins

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• {{UCSC gene info|CEBPB}}
• {{MeshName|CEBPB+protein,+human}}
• {{FactorBook|CEBPB}}

{{NLM content}}

{{PDB Gallery|geneid=1051}}

{{Transcription factors|g1}}

Category:Transcription factors