CEBPB
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CCAAT/增强子结合蛋白β,简称C/EBP-β或CEBPB,是一种在人体中由CEBPB基因编码的蛋白质。[5][6]
功能
这种无内含子基因编码的蛋白质是一种bZIP转录因子,可以作为同源二聚体与某些DNA调控区域结合。它还可以与相关蛋白 C/EBP-α、C/EBP-δ和C/EBP-γ形成异二聚体。编码的蛋白质在调节涉及免疫和炎症反应的基因中很重要,并且已显示与IL-6基因中的IL-1反应元件以及几种急性期和细胞因子基因的调节区域结合。此外,编码的蛋白质可以结合启动子和上游元件并刺激I型胶原蛋白基因的表达。[7]
CEBPB对正常的巨噬细胞功能至关重要,巨噬细胞是一种重要的免疫细胞亚型;无法表达CEBPB的小鼠具有无法分化(特化)的巨噬细胞,因此无法执行其所有生物学功能——包括巨噬细胞介导的肌肉修复。[8]观察工作表明,血液白细胞中CEBPB的表达与人体肌肉力量呈正相关,[9]强调了免疫系统,特别是巨噬细胞在维持肌肉功能中的重要性。
CEBPB基因的功能可以通过基于独立验证的siRNA敲低来有效检查。[10]
靶基因
CEBPB能够增加几个靶基因的表达。其中,一些在神经系统中具有特定作用,如前速激肽原-1基因,产生P物质和神经激肽A[11]以及负责生物合成重要神经递质乙酰胆碱的胆碱乙酰转移酶。[12]其他目标包括编码细胞因子的基因,例如IL-6、[13]IL-4、[14]IL-5、[15]和肿瘤坏死因子-α。[16]还发现编码赋予细胞多药抗性的转运蛋白的基因被CEBPB激活。这样的基因包括ABCC2[17]和ABCB1。[18]
相互作用
CEBPB已被证明可以与以下物质相互作用:
- CREB1[19]
- CRSP3[20]
- DDIT3[21][22]
- EP300[23]
- 雌激素受体α[24][25]
- 糖皮质激素受体[24]
- HMGA1[26]
- HSF1[27]
- 核仁连续体磷蛋白1[28]
- RELA[29][30]
- 血清反应因子[31][32]
- SMARCA2[33]
- Sp1 transcription factor[26][34]
- TRIM28,[35][36]
- EGR1[37]
参见
参考文献
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000172216 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000056501 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J. 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. Jul 1992, 13 (2): 293–300. PMID 1535333. doi:10.1016/0888-7543(92)90245-N.
- ^ Cao Z, Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. Oct 1991, 5 (9): 1538–52. PMID 1840554. doi:10.1101/gad.5.9.1538
.
- ^ Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta.
- ^ Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG, Rosenthal N, Nerlov C. A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proc. Natl. Acad. Sci. U.S.A. 2009, 106 (41): 17475–80. Bibcode:2009PNAS..10617475R. PMC 2762675
. PMID 19805133. doi:10.1073/pnas.0908641106
.
- ^ Harries LW, Pilling LC, Hernandez LD, Bradley-Smith R, Henley W, Singleton AB, Guralnik JM, Bandinelli S, Ferrucci L, Melzer D. CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength. Aging Cell. 2012, 11 (2): 262–8. PMC 3486692
. PMID 22152057. doi:10.1111/j.1474-9726.2011.00782.x.
- ^ Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs. Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments. Molecular Therapy: Nucleic Acids. 2016-01-01, 5 (9): e366. ISSN 2162-2531. PMC 5056990
. PMID 27673562. doi:10.1038/mtna.2016.66 (英语).
- ^ Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR. C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones. J. Neurochem. September 2006, 98 (5): 1390–9. PMID 16771829. S2CID 36225447. doi:10.1111/j.1471-4159.2006.03957.x.
- ^ Robert I, Sutter A, Quirin-Stricker C. Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta. Brain Res. Mol. Brain Res. October 2002, 106 (1–2): 124–35. PMID 12393272. doi:10.1016/S0169-328X(02)00419-9.
- ^ Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H, Kishimoto T. Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood. January 1992, 79 (2): 460–6. PMID 1730090. doi:10.1182/blood.V79.2.460.460
.
- ^ Davydov IV, Krammer PH, Li-Weber M. Nuclear factor-IL6 activates the human IL-4 promoter in T cells. J. Immunol. December 1995, 155 (11): 5273–9. PMID 7594540.
- ^ van Dijk TB, Baltus B, Raaijmakers JA, Lammers JW, Koenderman L, de Groot RP. 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. September 1999, 163 (5): 2674–80. PMID 10453008.
- ^ Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F. Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins. Mol. Cell. Biol. February 2000, 20 (3): 912–8. PMC 85208
. PMID 10629048. doi:10.1128/MCB.20.3.912-918.2000.
- ^ Tanaka T, Uchiumi T, Hinoshita E, Inokuchi A, Toh S, Wada M, Takano H, Kohno K, Kuwano M. The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells. Hepatology. December 1999, 30 (6): 1507–12. PMID 10573531. S2CID 22514353. doi:10.1002/hep.510300617.
- ^ Chen GK, Sale S, Tan T, Ermoian RP, Sikic BI. 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. April 2004, 65 (4): 906–16. PMID 15044620. S2CID 86591291. doi:10.1124/mol.65.4.906.
- ^ 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. 2003, 23 (12): 4066–82. PMC 156132
. PMID 12773552. doi:10.1128/mcb.23.12.4066-4082.2003.
- ^ Mo X, Kowenz-Leutz E, Xu H, Leutz A. Ras induces mediator complex exchange on C/EBP beta. Mol. Cell. January 2004, 13 (2): 241–50. PMID 14759369. doi:10.1016/s1097-2765(03)00521-5
.
- ^ 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. April 2003, 541 (1–3): 33–9. PMID 12706815. S2CID 43792576. doi:10.1016/s0014-5793(03)00283-7
.
- ^ 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. June 1996, 271 (24): 14285–9. PMID 8662954. doi:10.1074/jbc.271.24.14285
.
- ^ Mink S, Haenig B, Klempnauer KH. Interaction and functional collaboration of p300 and C/EBPbeta. Mol. Cell. Biol. November 1997, 17 (11): 6609–17. PMC 232514
. PMID 9343424. doi:10.1128/mcb.17.11.6609.
- ^ 24.0 24.1 Boruk M, Savory JG, Haché RJ. AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor. Mol. Endocrinol. November 1998, 12 (11): 1749–63. PMID 9817600. doi:10.1210/mend.12.11.0191
.
- ^ 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. September 1995, 15 (9): 4971–9. PMC 230744
. PMID 7651415. doi:10.1128/mcb.15.9.4971.
- ^ 26.0 26.1 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. 2003, 23 (8): 2720–32. PMC 152545
. PMID 12665574. doi:10.1128/mcb.23.8.2720-2732.2003.
- ^ 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. April 2002, 277 (14): 11802–10. PMID 11801594. doi:10.1074/jbc.M109296200
.
- ^ 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. April 1998, 273 (17): 10784–91. PMID 9553145. doi:10.1074/jbc.273.17.10784
.
- ^ 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. June 2003, 278 (26): 23586–93. PMID 12707271. doi:10.1074/jbc.M211646200
.
- ^ 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. December 1997, 29 (12): 1525–39. PMID 9570146. doi:10.1016/s1357-2725(97)00083-6.
- ^ Hanlon M, Sealy L. Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta. J. Biol. Chem. May 1999, 274 (20): 14224–8. PMID 10318842. doi:10.1074/jbc.274.20.14224
.
- ^ Sealy L, Malone D, Pawlak M. Regulation of the cfos serum response element by C/EBPbeta. Mol. Cell. Biol. March 1997, 17 (3): 1744–55. PMC 231899
. PMID 9032301. doi:10.1128/mcb.17.3.1744.
- ^ Kowenz-Leutz E, Leutz A. A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes. Mol. Cell. November 1999, 4 (5): 735–43. PMID 10619021. doi:10.1016/s1097-2765(00)80384-6
.
- ^ 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. July 2003, 171 (2): 821–8. PMID 12847250. doi:10.4049/jimmunol.171.2.821
.
- ^ 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. 2001, 15 (22): 3023–38. PMC 312827
. PMID 11711437. doi:10.1101/gad.937201.
- ^ 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. October 1998, 18 (10): 5880–7. PMC 109174
. PMID 9742105. doi:10.1128/mcb.18.10.5880.
- ^ 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. November 2003, 278 (45): 44246–54. PMID 12947119. doi:10.1074/jbc.M305564200
.
外部链接
- Human CEBPB genome location and CEBPB gene details page in the UCSC Genome Browser.
- 醫學主題詞表(MeSH):CEBPB+protein,+human
- FactorBook CEBPB
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