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一种具有关键LXXLL特征基序的Stat1转录共抑制因子。

A transcriptional corepressor of Stat1 with an essential LXXLL signature motif.

作者信息

Liu B, Gross M, ten Hoeve J, Shuai K

机构信息

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, CA 90095, USA.

出版信息

Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3203-7. doi: 10.1073/pnas.051489598.

Abstract

Interferon (IFN) treatment induces tyrosine phosphorylation and nuclear translocation of Stat1 (signal transducer and activator of transcription) to activate or repress transcription. We report here that a member of the protein inhibitor of activated STAT family, PIASy, is a transcriptional corepressor of Stat1. IFN treatment triggers the in vivo interaction of Stat1 with PIASy, which represses Stat1-mediated gene activation without blocking the DNA binding activity of Stat1. An LXXLL coregulator signature motif located near the NH(2) terminus of PIASy, although not involved in the PIASy-Stat1 interaction, is required for the transrepression activity of PIASy. Our studies identify PIASy as a transcriptional corepressor of Stat1 and suggest that different PIAS proteins may repress STAT-mediated gene activation through distinct mechanisms.

摘要

干扰素(IFN)治疗可诱导信号转导及转录激活因子1(Stat1)的酪氨酸磷酸化和核转位,从而激活或抑制转录。我们在此报告,活化STAT蛋白家族的蛋白抑制剂成员PIASy是Stat1的转录共抑制因子。IFN治疗可触发Stat1与PIASy在体内的相互作用,PIASy可抑制Stat1介导的基因激活,但不阻断Stat1的DNA结合活性。PIASy氨基端附近的LXXLL共调节因子特征基序虽不参与PIASy与Stat1的相互作用,但却是PIASy反式抑制活性所必需的。我们的研究确定PIASy为Stat1的转录共抑制因子,并表明不同的PIAS蛋白可能通过不同机制抑制STAT介导的基因激活。

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