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E2F1

E2F transcription factor 1
PDB rendering based on 2aze.
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 E2F1; E2F-1; RBAP1; RBBP3; RBP3
扩展标识 遗传学：189971 鼠基因：101941 同源基因：3828 ChEMBL: 4382 GeneCards: E2F1 Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 1869 13555
Ensembl ENSG00000101412 ENSMUSG00000027490
UniProt Q01094 Q61501
mRNA序列 NM_005225 NM_007891
蛋白序列 NP_005216 NP_031917
基因位置 Chr 20:
32.26 – 32.27 Mb		 Chr 2:
154.56 – 154.57 Mb
PubMed查询 [1] [2]

转录因子E2F1是由人类E2F1基因编码出的蛋白质[1]。

该基因编码出的蛋白质是E2F转录因子家族中的成员。E2F家族在控制细胞周期及抑癌基因功能上起到重要作用，也是小DNA致癌病毒转化蛋白的靶点。E2F家族中的多个成员蛋白包含许多进化保守的结构域。这些结构域包括：DNA结合域、与受分化调控的转录因子蛋白（DP）之间相互作用的二聚化结构域、富含酸性氨基酸的转活化结构域以及位于转活化结构域中的抑癌蛋白关联结构域。该蛋白与其他两个成员E2F2及E2F3具有额外的周期蛋白结合结构域。该蛋白以细胞周期依赖性的模式优先与视网膜母细胞瘤蛋白pRB结合。它可以同时介导细胞增殖及p53-依赖/非依赖的细胞凋亡[2]。

转录

E2F1的启动子区有PAX8转录因子的结合序列，可促进E2F1的转录[3]。

相互作用

E2F1与下列蛋白具有相互作用：NCOA6[4]、视网膜母细胞瘤样蛋白1[5]、视网膜母细胞瘤蛋白[5][6][7][8][9][10][11]、GTF2H1[12]、SKP2[13] PURA,[14]、NPDC1[15]、Sp2转录因子[16]、Sp1转录因子[16][17][18]、CUL1[13] ARID3A,[19]、TOPBP1[20][21]、周期蛋白A1[22]、TP53BP1[8]、周期蛋白A2[23]、Sp4转录因子[16]、Sp3转录因子[16]、抗增殖蛋白[24][25][26][27]、NDN[11][28]、MDM4[29] TFDP1[10][19][30][31]及泛素C[32]。

另见

参考文献

  1. ^ Neuman E, Sellers WR, McNeil JA, Lawrence JB, Kaelin WG Jr. Structure and partial genomic sequence of the human E2F1 gene. Gene. December 1996, 173 (2): 163–9. PMID 8964493. doi:10.1016/0378-1119(96)00184-9. 
  2. ^ Entrez Gene: E2F1 E2F transcription factor 1. （原始内容存档于2019-10-16）. 
  3. ^ Li, C G; Nyman, J E; Braithwaite, A W; Eccles, M R. PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein. Oncogene. 2011, 30 (48): 4824–4834. ISSN 0950-9232. doi:10.1038/onc.2011.190. 
  4. ^ Kong, Hee Jeong; Yu Hyun Jung, Hong SunHwa, Park Min Jung, Choi Young Hyun, An Won Gun, Lee Jae Woon, Cheong JaeHun. Interaction and functional cooperation of the cancer-amplified transcriptional coactivator activating signal cointegrator-2 and E2F-1 in cell proliferation. Mol. Cancer Res. (United States). November 2003, 1 (13): 948–58. ISSN 1541-7786. PMID 14638867. 
  5. ^ 5.0 5.1 Dyson, N; Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K. Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1. J. Virol. (UNITED STATES). December 1993, 67 (12): 7641–7. ISSN 0022-538X. PMC 238233 可免费查阅. PMID 8230483. 
  6. ^ Nicolas, E; Ait-Si-Ali S, Trouche D. The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein. Nucleic Acids Res. (England). August 2001, 29 (15): 3131–6. PMC 55834 可免费查阅. PMID 11470869. doi:10.1093/nar/29.15.3131. 
  7. ^ Pardo, Patricia S; Leung James K, Lucchesi John C, Pereira-Smith Olivia M. MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. J. Biol. Chem. (United States). December 2002, 277 (52): 50860–6. ISSN 0021-9258. PMID 12397079. doi:10.1074/jbc.M203839200. 
  8. ^ 8.0 8.1 Choubey, D; Li S J, Datta B, Gutterman J U, Lengyel P. Inhibition of E2F-mediated transcription by p202. EMBO J. (ENGLAND). October 1996, 15 (20): 5668–78. ISSN 0261-4189. PMC 452311 可免费查阅. PMID 8896460. 
  9. ^ Fajas, L; Paul C, Zugasti O, Le Cam L, Polanowska J, Fabbrizio E, Medema R, Vignais M L, Sardet C. pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F. Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES). July 2000, 97 (14): 7738–43. ISSN 0027-8424. PMC 16614 可免费查阅. PMID 10869426. doi:10.1073/pnas.130198397. 
  10. ^ 10.0 10.1 Wu, C L; Zukerberg L R, Ngwu C, Harlow E, Lees J A. In vivo association of E2F and DP family proteins. Mol. Cell. Biol. (UNITED STATES). May 1995, 15 (5): 2536–46. ISSN 0270-7306. PMC 230484 可免费查阅. PMID 7739537. 
  11. ^ 11.0 11.1 Taniura, H; Taniguchi N, Hara M, Yoshikawa K. Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J. Biol. Chem. (UNITED STATES). January 1998, 273 (2): 720–8. ISSN 0021-9258. PMID 9422723. doi:10.1074/jbc.273.2.720. 
  12. ^ Vandel, L; Kouzarides T. Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase. EMBO J. (ENGLAND). August 1999, 18 (15): 4280–91. ISSN 0261-4189. PMC 1171504 可免费查阅. PMID 10428966. doi:10.1093/emboj/18.15.4280. 
  13. ^ 13.0 13.1 Marti, A; Wirbelauer C, Scheffner M, Krek W. Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. Nat. Cell Biol. (ENGLAND). May 1999, 1 (1): 14–9. ISSN 1465-7392. PMID 10559858. doi:10.1038/8984. 
  14. ^ Darbinian, N; Gallia G L, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K. Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1. Oncogene (ENGLAND). November 1999, 18 (46): 6398–402. ISSN 0950-9232. PMID 10597240. doi:10.1038/sj.onc.1203011. 
  15. ^ Sansal, I; Dupont E, Toru D, Evrard C, Rouget P. NPDC-1, a regulator of neural cell proliferation and differentiation, interacts with E2F-1, reduces its binding to DNA and modulates its transcriptional activity. Oncogene (ENGLAND). October 2000, 19 (43): 5000–9. ISSN 0950-9232. PMID 11042687. doi:10.1038/sj.onc.1203843. 
  16. ^ 16.0 16.1 16.2 16.3 Rotheneder, H; Geymayer S, Haidweger E. Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter. J. Mol. Biol. (ENGLAND). November 1999, 293 (5): 1005–15. ISSN 0022-2836. PMID 10547281. doi:10.1006/jmbi.1999.3213. 
  17. ^ Lin, S Y; Black A R, Kostic D, Pajovic S, Hoover C N, Azizkhan J C. Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction. Mol. Cell. Biol. (UNITED STATES). April 1996, 16 (4): 1668–75. ISSN 0270-7306. PMC 231153 可免费查阅. PMID 8657142. 
  18. ^ Karlseder, J; Rotheneder H, Wintersberger E. Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol. Cell. Biol. (UNITED STATES). April 1996, 16 (4): 1659–67. ISSN 0270-7306. PMC 231152 可免费查阅. PMID 8657141. 
  19. ^ 19.0 19.1 Suzuki, M; Okuyama S, Okamoto S, Shirasuna K, Nakajima T, Hachiya T, Nojima H, Sekiya S, Oda K. A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent transcription by forming a heterodimer. Oncogene (ENGLAND). August 1998, 17 (7): 853–65. ISSN 0950-9232. PMID 9780002. doi:10.1038/sj.onc.1202163. 
  20. ^ Liu, Kang; Lin Fang-Tsyr, Ruppert J Michael, Lin Weei-Chin. Regulation of E2F1 by BRCT domain-containing protein TopBP1. Mol. Cell. Biol. (United States). May 2003, 23 (9): 3287–304. ISSN 0270-7306. PMC 153207 可免费查阅. PMID 12697828. doi:10.1128/MCB.23.9.3287-3304.2003. 
  21. ^ Yu, Xiaochun; Chini Claudia Christiano Silva, He Miao, Mer Georges, Chen Junjie. The BRCT domain is a phospho-protein binding domain. Science (United States). October 2003, 302 (5645): 639–42. PMID 14576433. doi:10.1126/science.1088753. 
  22. ^ Yang, R; Müller C, Huynh V, Fung Y K, Yee A S, Koeffler H P. Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. Mol. Cell. Biol. (UNITED STATES). March 1999, 19 (3): 2400–7. ISSN 0270-7306. PMC 84032 可免费查阅. PMID 10022926. 
  23. ^ Xu, M; Sheppard K A, Peng C Y, Yee A S, Piwnica-Worms H. Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol. Cell. Biol. (UNITED STATES). December 1994, 14 (12): 8420–31. ISSN 0270-7306. PMC 359381 可免费查阅. PMID 7969176. 
  24. ^ Joshi, Bharat; Ko Danette, Ordonez-Ercan Dalia, Chellappan Srikumar P. A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis. Biochem. Biophys. Res. Commun. (United States). December 2003, 312 (2): 459–66. ISSN 0006-291X. PMID 14637159. doi:10.1016/j.bbrc.2003.10.148. 
  25. ^ Fusaro, Gina; Dasgupta Piyali, Rastogi Shipra, Joshi Bharat, Chellappan Srikumar. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. J. Biol. Chem. (United States). November 2003, 278 (48): 47853–61. ISSN 0021-9258. PMID 14500729. doi:10.1074/jbc.M305171200. 
  26. ^ Wang, Sheng; Zhang Baohua, Faller Douglas V. Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth. EMBO J. (England). June 2002, 21 (12): 3019–28. ISSN 0261-4189. PMC 126057 可免费查阅. PMID 12065415. doi:10.1093/emboj/cdf302. 
  27. ^ Wang, S; Nath N, Fusaro G, Chellappan S. Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. Mol. Cell. Biol. (UNITED STATES). November 1999, 19 (11): 7447–60. ISSN 0270-7306. PMC 84738 可免费查阅. PMID 10523633. 
  28. ^ Kuwako, Ken-ichiro; Taniura Hideo, Yoshikawa Kazuaki. Necdin-related MAGE proteins differentially interact with the E2F1 transcription factor and the p75 neurotrophin receptor. J. Biol. Chem. (United States). January 2004, 279 (3): 1703–12. ISSN 0021-9258. PMID 14593116. doi:10.1074/jbc.M308454200. 
  29. ^ Strachan, Gordon D; Jordan-Sciutto Kelly L, Rallapalli Ravikumar, Tuan Rocky S, Hall David J. The E2F-1 transcription factor is negatively regulated by its interaction with the MDMX protein. J. Cell. Biochem. (United States). February 2003, 88 (3): 557–68. ISSN 0730-2312. PMID 12532331. doi:10.1002/jcb.10318. 
  30. ^ Sardet, C; Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg R A. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES). March 1995, 92 (6): 2403–7. ISSN 0027-8424. PMC 42492 可免费查阅. PMID 7892279. doi:10.1073/pnas.92.6.2403. 
  31. ^ Helin, K; Wu C L, Fattaey A R, Lees J A, Dynlacht B D, Ngwu C, Harlow E. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation. Genes Dev. (UNITED STATES). October 1993, 7 (10): 1850–61. ISSN 0890-9369. PMID 8405995. doi:10.1101/gad.7.10.1850. 
  32. ^ Zhou, Fangfang; Zhang Long, Wang Aijun, Song Bo, Gong Kai, Zhang Lihai, Hu Min, Zhang Xiufang, Zhao Nanming, Gong Yandao. The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation. J. Biol. Chem. (United States). May 2008, 283 (21): 14506–15. ISSN 0021-9258. PMID 18367454. doi:10.1074/jbc.M706136200. 

PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells.[永久失效連結]

深入阅读

  • Dupont E, Sansal I, Toru D; et al. [Identification of NPDC-1, gene involved in the control of proliferation and differentiation of neural and glial precursors]. C. R. Seances Soc. Biol. Fil. 1997, 191 (1): 95–104. PMID 9181131. 
  • Stevens C, La Thangue NB. The emerging role of E2F-1 in the DNA damage response and checkpoint control.. DNA Repair (Amst.). 2005, 3 (8-9): 1071–9. PMID 15279795. doi:10.1016/j.dnarep.2004.03.034. 
  • Zhang Z, Wang H, Li M; et al. Novel MDM2 p53-independent functions identified through RNA silencing technologies.. Ann. N. Y. Acad. Sci. 2006, 1058 (1): 205–14. PMID 16394138. doi:10.1196/annals.1359.030. 
  • Schild C, Wirth M, Reichert M, Schmid RM, Saur D, Schneider G. PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells. Mol. Carcinog. July 2009, 48 (12): 1149–58. PMID 19603422. doi:10.1002/mc.20569. 

外部链接

E2F1引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

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