CEBPB

CCAAT/增強子結合蛋白β，簡稱C/EBP-β或CEBPB，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 直系同源搜尋: PDBe RCSB PDBID列表 1GTW、​1GU4、​1GU5、​1H88、​1H89、​1H8A、​1HJB、​1IO4、​2E42、​2E43
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ID	OMIM：189965 MGI：88373 HomoloGene：3807 GeneCards：CEBPB
基因位置（人類） 染色體 20號染色體[1] 基因座 20q13.13 起始 50,190,830 bp[1] 終止 50,192,668 bp[1]
基因位置（小鼠） 染色體 小鼠2號染色體[2] 基因座 2 H3|2 87.58 cM 起始 167,530,835 bp[2] 終止 167,532,338 bp[2]
RNA表達模式
查閱更多表達數據
基因本體 分子功能 • DNA結合 • sequence-specific DNA binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding • protein homodimerization activity • DNA結合轉錄因子活性 • DNA-binding transcription activator activity, RNA polymerase II-specific • 轉錄因子結合 • histone deacetylase binding • chromatin binding • RNA polymerase II cis-regulatory region sequence-specific DNA binding • 激酶結合 • 血漿蛋白結合 • histone acetyltransferase binding • ubiquitin-like protein ligase binding • protein heterodimerization activity • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • RNA polymerase II core promoter sequence-specific DNA binding • DNA結合轉錄阻遏物活性，RNA聚合酶II特異性 • DNA-binding transcription factor activity, RNA polymerase II-specific • glucocorticoid receptor binding 細胞組分 • 細胞質 • nuclear matrix • CHOP-C/EBP complex • 核質 • 細胞核 • condensed chromosome, centromeric region • RNA polymerase II transcription regulator complex 生物學過程 • negative regulation of neuron apoptotic process • mammary gland epithelial cell proliferation • 細胞分化 • regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • cellular response to organic cyclic compound • embryonic placenta development • 記憶 • positive regulation of interleukin-4 production • response to endoplasmic reticulum stress • mammary gland epithelial cell differentiation • transcription, DNA-templated • positive regulation of transcription, DNA-templated • negative regulation of T cell proliferation • liver regeneration • positive regulation of osteoblast differentiation • hepatocyte proliferation • response to lipopolysaccharide • regulation of osteoclast differentiation • defense response to bacterium • 急性期反應 • 免疫反應 • neuron differentiation • cellular response to interleukin-1 • brown fat cell differentiation • cellular response to amino acid stimulus • ovarian follicle development • liver development • inflammatory response • negative regulation of transcription, DNA-templated • positive regulation of fat cell differentiation • cellular response to lipopolysaccharide • fat cell differentiation • positive regulation of transcription by RNA polymerase II • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • transcription by RNA polymerase II • granuloma formation • T-helper 1 cell activation • negative regulation of transcription by RNA polymerase II • regulation of odontoblast differentiation • positive regulation of biomineral tissue development • positive regulation of sodium-dependent phosphate transport • positive regulation of inflammatory response • positive regulation of cold-induced thermogenesis • regulation of dendritic cell differentiation Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	1051	12608
Ensembl	ENSG00000172216	ENSMUSG00000056501
UniProt	P17676	P28033
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 Mb	Chr 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

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-α、C/EBP-δ和C/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，血液白血球中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

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物質和神經激肽A^[11]以及負責生物合成重要神經遞質乙酰膽鹼的膽鹼乙酰轉移酶。^[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]和腫瘤壞死因子-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活化。這樣的基因包括ABCC2^[17]和ABCB1。^[18]

相互作用

CEBPB已被證明可以與以下物質相互作用：

• CREB1^[19]
• CRSP3^[20]
• DDIT3^[21][22]
• EP300^[23]
• 雌激素受體α^[24][25]
• 糖皮質激素受體^[24]
• HMGA1^[26]
• HSF1^[27]
• 核仁連續體磷蛋白1^[28]
• RELA^[29][30]
• 血清反應因子^[31][32]
• SMARCA2^[33]
• Sp1 transcription factor^[26][34]
• TRIM28,^[35][36]
• EGR1^[37]

參見

• Ccaat-enhancer-binding proteins

參考文獻

1. GRCh38: Ensembl release 89: ENSG00000172216 - Ensembl, May 2017
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）.
11. 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.
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. 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. 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 .
30. 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.
31. 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 .
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 .
34. 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 .
35. 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.
36. 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.
37. 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 .

外部連結

• Human CEBPB genome location and CEBPB gene details page in the UCSC Genome Browser（英語：UCSC Genome Browser）.
• 醫學主題詞表（MeSH）：CEBPB+protein,+human
• FactorBook CEBPB