CEBPB

位於20號人類染色體的基因

CCAAT/增強子結合蛋白β,簡稱C/EBP-βCEBPB,是一種在人體中由CEBPB基因編碼的蛋白質[5][6]

CEBPB
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
別名CEBPB;, C/EBP-beta, IL6DBP, NF-IL6, TCF5, CCAAT/enhancer binding protein beta, CCAAT enhancer binding protein beta
外部IDOMIM189965 MGI88373 HomoloGene3807 GeneCardsCEBPB
基因位置(人類
20號染色體
染色體20號染色體[1]
20號染色體
CEBPB的基因位置
CEBPB的基因位置
基因座20q13.13起始50,190,830 bp[1]
終止50,192,668 bp[1]
RNA表達模式
查閱更多表達數據
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_005194
​NM_001285878
​NM_001285879

NM_001287738
​NM_001287739
​NM_009883

蛋白序列

NP_001272807
​NP_001272808
​NP_005185

NP_001274667
​NP_001274668
​NP_034013

基因位置​(UCSC)Chr 20: 50.19 – 50.19 MbChr 2: 167.53 – 167.53 Mb
PubMed​查找[3][4]
維基數據
檢視/編輯人類檢視/編輯小鼠

功能

編輯

這種無內含子基因編碼的蛋白質是一種bZIP轉錄因子,可以作為同源二聚體與某些DNA調控區域結合。它還可以與相關蛋白 C/EBP-αC/EBP-δC/EBP-γ形成異二聚體。編碼的蛋白質在調節涉及免疫和炎症反應的基因中很重要,並且已顯示與IL-6基因中的IL-1反應元件以及幾種急性期和細胞因子基因的調節區域結合。此外,編碼的蛋白質可以結合啟動子和上游元件並刺激I型膠原蛋白基因的表達。[7]

CEBPB對正常的巨噬細胞功能至關重要,巨噬細胞是一種重要的免疫細胞亞型;無法表達CEBPB的小鼠具有無法分化(特化)的巨噬細胞,因此無法執行其所有生物學功能——包括巨噬細胞介導的肌肉修復。[8]觀察工作表明,血液白細胞中CEBPB的表達與人體肌肉力量呈正相關,[9]強調了免疫系統,特別是巨噬細胞在維持肌肉功能中的重要性。

CEBPB基因的功能可以通過基於獨立驗證的siRNA敲低來有效檢查。[10]

靶基因

編輯

CEBPB能夠增加幾個靶基因的表達。其中,一些在神經系統中具有特定作用,如前速激肽原-1基因,產生P物質神經激肽A[11]以及負責生物合成重要神經遞質乙酰膽鹼膽鹼乙酰轉移酶[12]其他目標包括編碼細胞因子的基因,例如IL-6[13]IL-4[14]IL-5[15]腫瘤壞死因子-α[16]還發現編碼賦予細胞多藥抗性的轉運蛋白的基因被CEBPB激活。這樣的基因包括ABCC2[17]ABCB1[18]

相互作用

編輯

CEBPB已被證明可以與以下物質相互作用:

參見

編輯

參考文獻

編輯
  1. ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000172216 - Ensembl, May 2017
  2. ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000056501 - Ensembl, May 2017
  3. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  4. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ 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. 
  6. ^ 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 . 
  7. ^ Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta. 
  8. ^ 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 . 
  9. ^ 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. 
  10. ^ 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 (英語). 
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  12. ^ 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. 
  13. ^ 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 . 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ 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. 
  19. ^ 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. 
  20. ^ 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 . 
  21. ^ 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 . 
  22. ^ 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 . 
  23. ^ 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. ^ 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 . 
  25. ^ 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. ^ 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. 
  27. ^ 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 . 
  28. ^ 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 . 
  29. ^ 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 . 
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  32. ^ 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. 
  33. ^ 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 . 
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外部連結

編輯