CEBPB

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CCAAT/enhancer binding protein (C/EBP), beta
1gtw.png
Crystal structure of C/EBPbeta bZip domain (pink helices) bound to DNA(spheres.) PDB entry 1gtw.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CEBPB ; C/EBP-beta; CRP2; IL6DBP; LAP; NF-IL6; TCF5
External IDs OMIM189965 MGI88373 HomoloGene3807 GeneCards: CEBPB Gene
RNA expression pattern
PBB GE CEBPB 212501 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1051 12608
Ensembl ENSG00000172216 ENSMUSG00000056501
UniProt P17676 P28033
RefSeq (mRNA) NM_005194 NM_009883
RefSeq (protein) NP_005185 NP_034013
Location (UCSC) Chr 20:
48.81 – 48.81 Mb
Chr 2:
167.69 – 167.69 Mb
PubMed search [1] [2]

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

Function[edit]

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.

Target genes[edit]

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 gene, giving rise to substance P and neurokinin A[6] and the choline acetyltransferase responsible for the biosynthesis of the important neurotransmitter acetylcholine.[7] Other targets include genes coding for cytokines such as IL-6,[8] IL-4,[9] IL-5,[10] and TNF-alpha.[11] 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[12] and ABCB1.[13]

Interactions[edit]

CEBPB has been shown to interact with:

See also[edit]


References[edit]

  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. 
  6. ^ 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. 
  7. ^ Robert I, Sutter A, Quirin-Stricker C (October 2002). "Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta". Brain Res. Mol. Brain Res. 106 (1–2): 124–35. doi:10.1016/S0169-328X(02)00419-9. PMID 12393272. 
  8. ^ Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H, Kishimoto T (January 1992). "Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6". Blood 79 (2): 460–6. PMID 1730090. 
  9. ^ Davydov IV, Krammer PH, Li-Weber M (December 1995). "Nuclear factor-IL6 activates the human IL-4 promoter in T cells". J. Immunol. 155 (11): 5273–9. PMID 7594540. 
  10. ^ van Dijk TB, Baltus B, Raaijmakers JA, Lammers JW, Koenderman L, de Groot RP (September 1999). "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". J. Immunol. 163 (5): 2674–80. PMID 10453008. 
  11. ^ 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. 
  12. ^ Tanaka T, Uchiumi T, Hinoshita E, Inokuchi A, Toh S, Wada M, Takano H, Kohno K, Kuwano M (December 1999). "The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells". Hepatology 30 (6): 1507–12. doi:10.1002/hep.510300617. PMID 10573531. 
  13. ^ Chen GK, Sale S, Tan T, Ermoian RP, Sikic BI (April 2004). "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". Mol. Pharmacol. 65 (4): 906–16. doi:10.1124/mol.65.4.906. PMID 15044620. 
  14. ^ Chen Y, Zhuang S, Cassenaer S, Casteel DE, Gudi T, Boss GR, Pilz RB. "Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires cooperation between CREB and C/EBP-beta". Mol. Cell. Biol. 23 (12): 4066–82. doi:10.1128/mcb.23.12.4066-4082.2003. PMC 156132. PMID 12773552. 
  15. ^ Mo X, Kowenz-Leutz E, Xu H, Leutz A. "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. 
  16. ^ Hattori T, Ohoka N, Hayashi H, Onozaki K. "C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform". FEBS Lett. 541 (1-3): 33–9. doi:10.1016/s0014-5793(03)00283-7. PMID 12706815. 
  17. ^ Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ. "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". J. Biol. Chem. 271 (24): 14285–9. doi:10.1074/jbc.271.24.14285. PMID 8662954. 
  18. ^ Mink S, Haenig B, Klempnauer KH. "Interaction and functional collaboration of p300 and C/EBPbeta". Mol. Cell. Biol. 17 (11): 6609–17. PMC 232514. PMID 9343424. 
  19. ^ a b Boruk M, Savory JG, Haché RJ. "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. 
  20. ^ Stein B, Yang MX. "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. 
  21. ^ a b Foti D, Iuliano R, Chiefari E, Brunetti A. "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Mol. Cell. Biol. 23 (8): 2720–32. doi:10.1128/mcb.23.8.2720-2732.2003. PMC 152545. PMID 12665574. 
  22. ^ Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK. "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. 
  23. ^ Miau LH, Chang CJ, Shen BJ, Tsai WH, Lee SC. "Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation". J. Biol. Chem. 273 (17): 10784–91. doi:10.1074/jbc.273.17.10784. PMID 9553145. 
  24. ^ Weber M, Sydlik C, Quirling M, Nothdurfter C, Zwergal A, Heiss P, Bell S, Neumeier D, Ziegler-Heitbrock HW, Brand K. "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. 
  25. ^ Xia C, Cheshire JK, Patel H, Woo P. "Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes". Int. J. Biochem. Cell Biol. 29 (12): 1525–39. doi:10.1016/s1357-2725(97)00083-6. PMID 9570146. 
  26. ^ Hanlon M, Sealy L. "Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta". J. Biol. Chem. 274 (20): 14224–8. doi:10.1074/jbc.274.20.14224. PMID 10318842. 
  27. ^ Sealy L, Malone D, Pawlak M. "Regulation of the cfos serum response element by C/EBPbeta". Mol. Cell. Biol. 17 (3): 1744–55. PMC 231899. PMID 9032301. 
  28. ^ Kowenz-Leutz E, Leutz A. "A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes". Mol. Cell 4 (5): 735–43. doi:10.1016/s1097-2765(00)80384-6. PMID 10619021. 
  29. ^ Liu YW, Tseng HP, Chen LC, Chen BK, Chang WC. "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". J. Immunol. 171 (2): 821–8. doi:10.4049/jimmunol.171.2.821. PMID 12847250. 
  30. ^ Rooney JW, Calame KL. "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. 
  31. ^ Chang CJ, Chen YL, Lee SC. "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. PMC 109174. PMID 9742105. 
  32. ^ Zhang F, Lin M, Abidi P, Thiel G, Liu J. "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". J. Biol. Chem. 278 (45): 44246–54. doi:10.1074/jbc.M305564200. PMID 12947119. 

External links[edit]

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