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通用转录因子TFIIA的一次改造

A facelift for the general transcription factor TFIIA.

作者信息

Høiby Torill, Zhou Huiqing, Mitsiou Dimitra J, Stunnenberg Hendrik G

机构信息

NCMLS, Department of Molecular Biology, 191, Radboud University of Nijmegen, PO Box 91001, 6500 HB Nijmegen, The Netherlands.

出版信息

Biochim Biophys Acta. 2007 Jul-Aug;1769(7-8):429-36. doi: 10.1016/j.bbaexp.2007.04.008. Epub 2007 May 5.

DOI:10.1016/j.bbaexp.2007.04.008
PMID:17560669
Abstract

TFIIA was classified as a general transcription factor when it was first identified. Since then it has been debated to what extent it can actually be regarded as "general". The most notable feature of TFIIA is the proteolytical cleavage of the TFIIAalphabeta into a TFIIAalpha and TFIIAbeta moiety which has long remained a mystery. Recent studies have showed that TFIIA is cleaved by Taspase1 which was initially identified as the protease for the proto-oncogene MLL. Cleavage of TFIIA does not appear to serve as a step required for its activation as the uncleaved TFIIA in the Taspase1 knock-outs adequately support bulk transcription. Instead, cleavage of TFIIA seems to affect its turn-over and may be a part of an intricate degradation mechanism that allows fine-tuning of cellular levels of TFIIA. Cleavage might also be responsible for switching transcription program as the uncleaved and cleaved TFIIA might have distinct promoter specificity during development and differentiation. This review will focus on functional characteristics of TFIIA and discuss novel insights in the role of this elusive transcription factor.

摘要

TFIIA最初被鉴定时被归类为一种通用转录因子。从那时起,关于它在何种程度上可被真正视为“通用”一直存在争议。TFIIA最显著的特征是TFIIAαβ被蛋白水解切割成TFIIAα和TFIIAβ部分,这一现象长期以来一直是个谜。最近的研究表明,TFIIA被Taspase1切割,Taspase1最初被鉴定为原癌基因MLL的蛋白酶。TFIIA的切割似乎并不是其激活所必需的步骤,因为在Taspase1基因敲除中未切割的TFIIA能够充分支持大量转录。相反,TFIIA的切割似乎影响其周转,可能是一种复杂降解机制的一部分,该机制允许对TFIIA的细胞水平进行微调。切割也可能负责切换转录程序,因为未切割和切割的TFIIA在发育和分化过程中可能具有不同的启动子特异性。本综述将重点关注TFIIA的功能特性,并讨论这种难以捉摸的转录因子作用的新见解。

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