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]
↑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. PMID1535333.
↑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. PMID1840554.
↑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. PMID16771829.
↑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. PMID12393272.
↑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. PMID1730090.
↑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. PMID7594540.
↑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. PMID10453008.
↑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. PMID10573531.
↑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. PMID15044620.
↑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. PMID14759369.
↑Hattori T, Ohoka N, Hayashi H, Onozaki K (April 2003). "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. PMID12706815.
↑Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ (June 1996). "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. PMID8662954.
↑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. PMID11801594.
↑Miau LH, Chang CJ, Shen BJ, Tsai WH, Lee SC (April 1998). "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. PMID9553145.
↑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. PMID12707271.
↑Xia C, Cheshire JK, Patel H, Woo P (December 1997). "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. PMID9570146.
↑Hanlon M, Sealy L (May 1999). "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. PMID10318842.
↑Kowenz-Leutz E, Leutz A (November 1999). "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. PMID10619021.
↑Liu YW, Tseng HP, Chen LC, Chen BK, Chang WC (July 2003). "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. PMID12847250.
↑Zhang F, Lin M, Abidi P, Thiel G, Liu J (November 2003). "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. PMID12947119.
1io4: CRYSTAL STRUCTURE OF RUNX-1/AML1/CBFALPHA RUNT DOMAIN-CBFBETA CORE DOMAIN HETERODIMER AND C/EBPBETA BZIP HOMODIMER BOUND TO A DNA FRAGMENT FROM THE CSF-1R PROMOTER