CoREST represses the heat shock response mediated by HSF1
CoREST represses the heat shock response mediated by HSF1
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DOI：
10.1016/j.molcel.2008.06.015
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发表时间：
2008-07-25
期刊：
影响因子：
16
通讯作者：
Andres, Maria Estela
中科院分区：
文献类型：
--
作者：
Gomez, Andrea V.;Galleguillos, Danny;Andres, Maria Estela
细胞中的应激反应涉及应激基因的快速和瞬时转录激活。研究表明，Hsp70作为热休克因子1（HSF1）的辅阻遏物，在应激反应的减弱过程中限制了自身的转录激活。在这里，我们表明，转录辅阻遏物CoREST与热休克蛋白70相互作用。通过这种相互作用，CoREST抑制热休克蛋白70启动子的HSF1依赖性和热休克依赖性转录激活。在表达针对CoREST的短发夹RNA的细胞中，Hsp70不能抑制HSF1依赖的转录。CoREST水平的降低也引起了Hsp70蛋白水平的显著增加和HSF1依赖的Hsp70启动子的反式激活的增加。通过染色质免疫沉淀试验，我们表明，CoREST是绑定到热休克反应过程中的热休克蛋白70基因启动子在基础条件下，其结合增加。总之，我们证明了CoREST是热休克应激反应的关键调节因子。
The stress response in cells involves a rapid and transient transcriptional activation of stress genes. It has been shown that Hsp70 limits its own transcriptional activation functioning as a corepressor of heat shock factor 1 (HSF1) during the attenuation of the stress response. Here we show that the transcriptional corepressor CoREST interacts with Hsp70. Through this interaction, CoREST represses bot HSF1-dependent and heat shock-dependent transcriptional activation of the hsp70 promoter. In cells expressing short hairpin RNAs directed against CoREST, Hsp70 cannot repress HSF1-dependent transcription. A reduction of CoREST levels also provoked a significant increase of Hsp70 protein levels and an increase of HSF1-dependent transactivation of hsp70 promoter. Via chromatin immunoprecipitation assays we show that CoREST is bound to the hsp70 gene promoter under basal conditions and that its binding increases during heat shock response. In conclusion, we demonstrated that CoREST is a key regulator of the heat shock stress response.