Biology:CEBPB

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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]

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.

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]

Enhancer Binding-Protein

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" [39].[15]  Anthough it was also mentioned that eachof 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"[38].[16]

Cancer

CEBPB is a type of CEBP transcript. CEBPB[17] 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.

Interactions

CEBPB has been shown to interact with:


See also

References

  1. ↑ "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. June 1992. doi:10.1016/0888-7543(92)90245-N. PMID 1535333. 
  2. ↑ "Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells". Genes & Development 5 (9): 1538–1552. September 1991. doi:10.1101/gad.5.9.1538. PMID 1840554. 
  3. ↑ "Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1051. 
  4. ↑ "A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair". Proceedings of the National Academy of Sciences of the United States of America 106 (41): 17475–17480. October 2009. doi:10.1073/pnas.0908641106. PMID 19805133. Bibcode: 2009PNAS..10617475R. 
  5. ↑ "CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength". Aging Cell 11 (2): 262–268. April 2012. doi:10.1111/j.1474-9726.2011.00782.x. PMID 22152057. 
  6. ↑ "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy. Nucleic Acids 5 (9): e366. September 2016. doi:10.1038/mtna.2016.66. PMID 27673562. 
  7. ↑ "C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones". Journal of Neurochemistry 98 (5): 1390–1399. September 2006. doi:10.1111/j.1471-4159.2006.03957.x. PMID 16771829. 
  8. ↑ "Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta". Brain Research. Molecular Brain Research 106 (1–2): 124–135. October 2002. doi:10.1016/S0169-328X(02)00419-9. PMID 12393272. 
  9. ↑ "Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6". Blood 79 (2): 460–466. January 1992. doi:10.1182/blood.V79.2.460.460. PMID 1730090. 
  10. ↑ "Nuclear factor-IL6 activates the human IL-4 promoter in T cells". Journal of Immunology 155 (11): 5273–5279. December 1995. doi:10.4049/jimmunol.155.11.5273. PMID 7594540. 
  11. ↑ "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 of Immunology 163 (5): 2674–2680. September 1999. doi:10.4049/jimmunol.163.5.2674. PMID 10453008. 
  12. ↑ "Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins". Molecular and Cellular Biology 20 (3): 912–918. February 2000. doi:10.1128/MCB.20.3.912-918.2000. PMID 10629048. 
  13. ↑ "The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells". Hepatology 30 (6): 1507–1512. December 1999. doi:10.1002/hep.510300617. PMID 10573531. 
  14. ↑ "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". Molecular Pharmacology 65 (4): 906–916. April 2004. doi:10.1124/mol.65.4.906. PMID 15044620. 
  15. ↑ "CEBPB protein expression summary - The Human Protein Atlas". https://www.proteinatlas.org/ENSG00000172216-CEBPB. 
  16. ↑ "Gene - CEBPB". https://maayanlab.cloud/Harmonizome/gene/CEBPB. 
  17. ↑ "CEBPB CCAAT enhancer binding protein beta [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/1051. 
  18. ↑ "Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires cooperation between CREB and C/EBP-beta". Molecular and Cellular Biology 23 (12): 4066–4082. June 2003. doi:10.1128/mcb.23.12.4066-4082.2003. PMID 12773552. 
  19. ↑ "Ras induces mediator complex exchange on C/EBP beta". Molecular Cell 13 (2): 241–250. January 2004. doi:10.1016/s1097-2765(03)00521-5. PMID 14759369. 
  20. ↑ "C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform". FEBS Letters 541 (1–3): 33–39. April 2003. doi:10.1016/s0014-5793(03)00283-7. PMID 12706815. 
  21. ↑ "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". The Journal of Biological Chemistry 271 (24): 14285–14289. June 1996. doi:10.1074/jbc.271.24.14285. PMID 8662954. 
  22. ↑ "Interaction and functional collaboration of p300 and C/EBPbeta". Molecular and Cellular Biology 17 (11): 6609–6617. November 1997. doi:10.1128/mcb.17.11.6609. PMID 9343424. 
  23. ↑ 23.0 23.1 "AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor". Molecular Endocrinology 12 (11): 1749–1763. November 1998. doi:10.1210/mend.12.11.0191. PMID 9817600. 
  24. ↑ "Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta". Molecular and Cellular Biology 15 (9): 4971–4979. September 1995. doi:10.1128/mcb.15.9.4971. PMID 7651415. 
  25. ↑ 25.0 25.1 "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Molecular and Cellular Biology 23 (8): 2720–2732. April 2003. doi:10.1128/mcb.23.8.2720-2732.2003. PMID 12665574. 
  26. ↑ "Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6". The Journal of Biological Chemistry 277 (14): 11802–11810. April 2002. doi:10.1074/jbc.M109296200. PMID 11801594. 
  27. ↑ "Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation". The Journal of Biological Chemistry 273 (17): 10784–10791. April 1998. doi:10.1074/jbc.273.17.10784. PMID 9553145. 
  28. ↑ "Transcriptional inhibition of interleukin-8 expression in tumor necrosis factor-tolerant cells: evidence for involvement of C/EBP beta". The Journal of Biological Chemistry 278 (26): 23586–23593. June 2003. doi:10.1074/jbc.M211646200. PMID 12707271. 
  29. ↑ "Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes". The International Journal of Biochemistry & Cell Biology 29 (12): 1525–1539. December 1997. doi:10.1016/s1357-2725(97)00083-6. PMID 9570146. 
  30. ↑ "Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta". The Journal of Biological Chemistry 274 (20): 14224–14228. May 1999. doi:10.1074/jbc.274.20.14224. PMID 10318842. 
  31. ↑ "Regulation of the cfos serum response element by C/EBPbeta". Molecular and Cellular Biology 17 (3): 1744–1755. March 1997. doi:10.1128/mcb.17.3.1744. PMID 9032301. 
  32. ↑ "A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes". Molecular Cell 4 (5): 735–743. November 1999. doi:10.1016/s1097-2765(00)80384-6. PMID 10619021. 
  33. ↑ "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 of Immunology 171 (2): 821–828. July 2003. doi:10.4049/jimmunol.171.2.821. PMID 12847250. 
  34. ↑ "TIF1beta functions as a coactivator for C/EBPbeta and is required for induced differentiation in the myelomonocytic cell line U937". Genes & Development 15 (22): 3023–3038. November 2001. doi:10.1101/gad.937201. PMID 11711437. 
  35. ↑ "Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression". Molecular and Cellular Biology 18 (10): 5880–5887. October 1998. doi:10.1128/mcb.18.10.5880. PMID 9742105. 
  36. ↑ "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". The Journal of Biological Chemistry 278 (45): 44246–44254. November 2003. doi:10.1074/jbc.M305564200. PMID 12947119. 

External links

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



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