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中介体

维基百科,自由的百科全书
中介体与一些周期蛋白依赖性激酶结合
酵母菌的中介体,可见其中MED14英语MED14蛋白结构多变的内在无序结构域

中介体(Mediator)旧称DRIPTRAP[1][2],是真核生物细胞核中启动基因转录所需的蛋白质复合体[3][4],于1990年由美国生物学家罗杰·科恩伯格发现[5][6]。中介体可与RNA聚合酶ⅡC端结构域转录因子结合[7],结合在基因的强化子启动子之间,组成转录前起始复合体。RNA转录起始后中介体和转录因子不会马上自启动子脱离,而会维持在该处以继续结合新的RNA聚合酶Ⅱ,开启新一轮的转录[3]

中介体的组成蛋白因物种而异[3],如酿酒酵母的中介体有21个核心蛋白,哺乳类的中介体则有约30个,许多中介体的蛋白具有内在无序结构域英语Intrinsically disordered proteins,为结构较为弹性的区域,可能有助于其改变结构以达成不同功能[8],除组成的核心蛋白外,中介体还会与一些周期蛋白依赖性激酶(CDK)结合,形成转录前起始复合体时与中介体结合的CDK会自其脱落,使RNA聚合酶Ⅱ得以与中介体结合[9]。中介体还会与一个非编码RNAncRNA-a结合,与其功能有关[10]

除了调控mRNA(RNA聚合酶Ⅱ)的转录外,还有研究显示酵母菌的中介体参与RNA聚合酶III转录tRNA的过程[11][12]。另外中介体可能还可维持中节端粒的结构[3],有些中介体的核心蛋白(MED15英语MED15MED23英语MED23MED25英语MED25)参与讯息传递路径,可能为各种讯息传递路径最终借由影响中介体的蛋白以调控基因表现[3][13][14]

参考文献

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  1. ^ Oda Y, Chalkley RJ, Burlingame AL, Bikle DD. The transcriptional coactivator DRIP/mediator complex is involved in vitamin D receptor function and regulates keratinocyte proliferation and differentiation.. J Invest Dermatol. 2010, 130 (10): 2377–88. PMC 4114506可免费查阅. PMID 20520624. doi:10.1038/jid.2010.148. 
  2. ^ Ito M, Okano HJ, Darnell RB, Roeder RG. The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development.. EMBO J. 2002, 21 (13): 3464–75. PMC 126097可免费查阅. PMID 12093747. doi:10.1093/emboj/cdf348. 
  3. ^ 3.0 3.1 3.2 3.3 3.4 Allen BL, Taatjes DJ. The Mediator complex: a central integrator of transcription. Nature Reviews Molecular Cell Biology. March 2015, 16 (3): 155–66. PMC 4963239可免费查阅. PMID 25693131. doi:10.1038/nrm3951. 
  4. ^ Biddick R, Young ET. Yeast mediator and its role in transcriptional regulation. Comptes Rendus Biologies. September 2005, 328 (9): 773–82. PMID 16168358. doi:10.1016/j.crvi.2005.03.004. 
  5. ^ Kelleher RJ, Flanagan PM, Kornberg RD. A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell. June 1990, 61 (7): 1209–15. PMID 2163759. doi:10.1016/0092-8674(90)90685-8. 
  6. ^ Flanagan PM, Kelleher RJ, Sayre MH, Tschochner H, Kornberg RD. A mediator required for activation of RNA polymerase II transcription in vitro. Nature. April 1991, 350 (6317): 436–8. Bibcode:1991Natur.350..436F. PMID 2011193. doi:10.1038/350436a0. 
  7. ^ Björklund S, Gustafsson CM. The yeast Mediator complex and its regulation. Trends in Biochemical Sciences. May 2005, 30 (5): 240–4. PMID 15896741. doi:10.1016/j.tibs.2005.03.008. 
  8. ^ Robinson PJ, Trnka MJ, Pellarin R, Greenberg CH, Bushnell DA, Davis R, Burlingame AL, Sali A, Kornberg RD. Molecular architecture of the yeast Mediator complex. eLife. September 2015, 4: e08719. PMC 4631838可免费查阅. PMID 26402457. doi:10.7554/eLife.08719. 
  9. ^ Petrenko, N; Jin, Y; Wong, KH; Struhl, K. Mediator Undergoes a Compositional Change during Transcriptional Activation.. Molecular Cell. 3 November 2016, 64 (3): 443–454. PMC 5096951可免费查阅. PMID 27773675. doi:10.1016/j.molcel.2016.09.015. 
  10. ^ Lai, F; et al. Activating RNAs associate with mediator to enhance chromatin architecture and transcription (PDF). Nature. 2013, 494 (7438): 497–501 [2021-05-23]. Bibcode:2013Natur.494..497L. PMC 4109059可免费查阅. PMID 23417068. doi:10.1038/nature11884. hdl:11858/00-001M-0000-0019-1122-4. (原始内容 (PDF)存档于2017-08-14). 
  11. ^ Carlsten, JO; Zhu X, López MD, Samuelsson T, Gustafsson CM. Loss of the Mediator subunit Med20 affects transcription of tRNA and other non-coding RNA genes in fission yeast. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. February 2016, 1859 (2): 339–347. PMID 26608234. doi:10.1016/j.bbagrm.2015.11.007. 
  12. ^ Uthe H, Vanselow JT, Schlosser A. Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae. Sci Rep. 2017, 7: 43584. Bibcode:2017NatSR...743584U. PMC 5327418可免费查阅. PMID 28240253. doi:10.1038/srep43584. 
  13. ^ Chen, Rong; Jiang, Hongling; Li, Lin; Zhai, Qingzhe; Qi, Linlin; Zhou, Wenkun; Liu, Xiaoqiang; Li, Hongmei; Zheng, Wenguang; Sun, Jiaqiang; Li, Chuanyou. The Arabidopsis Mediator Subunit MED25 Differentially Regulates Jasmonate and Abscisic Acid Signaling through Interacting with the MYC2 and ABI5 Transcription Factors. The Plant Cell. July 2012, 24 (7): 2898–2916. PMC 3426122可免费查阅. PMID 22822206. doi:10.1105/tpc.112.098277. 
  14. ^ Sun, Wenjing; Han, Hongyu; Deng, Lei; Sun, Chuanlong; Xu, Yiran; Lin, Lihao; Ren, Panrong; Zhao, Jiuhai; Zhai, Qingzhe; Li, Chuanyou. Mediator Subunit MED25 Physically Interacts with PHYTOCHROME INTERACTING FACTOR4 to Regulate Shade-Induced Hypocotyl Elongation in Tomato. Plant Physiology. November 2020, 184 (3): 1549–1562. PMC 7608172可免费查阅. PMID 32938743. doi:10.1104/pp.20.00587.