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中介體

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中介體與一些週期蛋白依賴性激酶結合
酵母菌的中介體,可見其中MED14英语MED14蛋白結構多變的內在無序結構域

中介體(Mediator)舊稱DRIPTRAP[1][2],是真核生物細胞核中啟動基因轉錄所需的蛋白質複合體[3][4],於1990年由美國生物學家罗杰·科恩伯格發現[5][6]。中介體可與RNA聚合酶ⅡC端結構域轉錄因子結合[7],結合在基因的強化子啟動子之間,組成轉錄前起始複合體。RNA轉錄起始後中介體和轉錄因子不會馬上自啟動子脫離,而會維持在該處以繼續結合新的RNA聚合酶Ⅱ,開啟新一輪的轉錄[3]

中介體的組成蛋白因物種而異[3],如釀酒酵母的中介體有21個核心蛋白,哺乳類的中介體則有約30個,許多中介體的蛋白具有內在無序結構域英语Intrinsically disordered proteins,為結構較為彈性的區域,可能有助於其改變結構以達成不同功能[8],除組成的核心蛋白外,中介體還會與一些週期蛋白依賴性激酶(CDK)結合,形成轉錄前起始複合體時與中介體結合的CDK會自其脫落,使RNA聚合酶Ⅱ得以與中介體結合[9]。中介體還會與一個非編碼RNAncRNA-a結合,與其功能有關[10]

除了調控mRNA(RNA聚合酶Ⅱ)的轉錄外,還有研究顯示酵母菌的中介體參與RNA聚合酶III轉錄tRNA的過程[11][12]。另外中介體可能還可維持中節端粒的結構[3],有些中介體的核心蛋白(MED15英语MED15MED23英语MED23MED25英语MED25)參與訊息傳遞路徑,可能為各種訊息傳遞路徑最終藉由影響中介體的蛋白以調控基因表現[3][13][14]

參考文獻

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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.