Requirement for Hsp90 and a CyP-40-type cyclophilin in negative regulation of the heat shock response
Requirement for Hsp90 and a CyP-40-type cyclophilin in negative regulation of the heat shock response
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DOI：
10.1074/jbc.273.30.18974
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发表时间：
1998-07-24
影响因子：
4.8
通讯作者：
Gaber, RF
中科院分区：
文献类型：
--
作者：
Duina, AA;Kalton, HM;Gaber, RF
热休克反应是一种高度保守的机制，使细胞能够承受各种应激条件。这种应答的激活的特征在于热休克蛋白（HSP）的合成增加，热休克蛋白（HSP）保护细胞蛋白免受应激诱导的变性。热休克转录因子（HSF）是应激条件下HSP表达增加所必需的，并且可以在含有Hsp 90分子伴侣机制的组分的复合物中发现，提高了热休克蛋白90参与调节热休克反应的可能性。为了测试这一点，我们已经评估了突变的影响，损害活动的热休克相关的事件在酿酒酵母的热休克90机制。突变，无论是降低Hsp 90蛋白的水平或消除Cpr 7，CyP-40型亲环蛋白所需的完整的Hsp 90功能，导致增加的HSF依赖的活动。遗传测试还显示，Hsp 90和Cpr 7协同作用，抑制来自HSF依赖性启动子的基因表达。有条件的热休克蛋白90活性的损失导致增加的热休克因子依赖的基因表达和收购的耐热表型。我们的研究结果表明，热休克蛋白90和Cpr 7所需的负调控的热休克反应在应力和非应力条件下，并建立一个特定的内源性作用的热休克蛋白90机器在S。啤酒。
The heat shock response is a highly conserved mechanism that allows cells to withstand a variety of stress conditions. Activation of this response is characterized by increased synthesis of heat shock proteins (HSPs), which protect cellular proteins from stress-induced denaturation, Heat shock transcription factors (HSFs) are required for increased expression of HSPs during stress conditions and can be found in complexes containing components of the Hsp90 molecular chaperone machinery, raising the possibility that Hsp90 is involved in regulation of the heat shock response. To test this, we have assessed the effects of mutations that impair activity of the Hsp90 machinery on heat shock related events in Saccharomyces cerevisiae. Mutations that either reduce the level of Hsp90 protein or eliminate Cpr7, a CyP-40-type cyclophilin required for full Hsp90 function, resulted in increased HSF-dependent activities. Genetic tests also revealed that Hsp90 and Cpr7 function synergistically to repress gene expression from HSF-dependent promoters. Conditional loss of Hsp90 activity resulted in both increased HSF-dependent gene expression and acquisition of a thermotolerant phenotype. Our results reveal that Hsp90 and Cpr7 are required for negative regulation of the heat shock response under both stress and nonstress conditions and establish a specific endogenous role for the Hsp90 machinery in S. cerevisiae.