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CCAAT/enhancer binding protein (C/EBP), beta
Crystal structure of C/EBPbeta bZip domain (pink helices) bound to DNA(spheres.) PDB entry 1gtw.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols CEBPB ; C/EBP-beta; IL6DBP; 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
Species Human Mouse
Entrez 1051 12608
Ensembl ENSG00000172216 ENSMUSG00000056501
UniProt P17676 P28033
RefSeq (mRNA) NM_001285878 NM_001287738
RefSeq (protein) NP_001272807 NP_001274667
Location (UCSC) Chr 20:
50.19 – 50.19 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]


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]


CEBPB has been shown to interact with:

See also[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 (November 1997). "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 (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. 
  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 (March 1997). "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 (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. 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.