MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells
MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells
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MED12 与热休克转录因子 HSF1 相互作用并招募 CDK8 促进哺乳动物细胞的热休克反应
DOI：
10.1002/1873-3468.14139
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Nakai Akira
中科院分区：
文献类型：
--
作者：
Srivastava Pratibha;Takii Ryosuke;Okada Mariko;Fujimoto Mitsuaki;Nakai Akira
激活且启动子结合的热休克转录因子 1 (HSF1) 在热休克时诱导 RNA 聚合酶 II 募集，果蝇和酵母中的核心介体促进了这一过程。另一个介导模块，CDK8激酶模块（CKM），由MED12和CDK8等四个亚基组成，在转录调节中发挥负向或正向作用；然而，其参与 HSF1 介导的转录仍不清楚。我们在此证明HSF1与MED12相互作用，并在哺乳动物细胞热休克期间将MED12和CDK8募集至HSP70启动子。 CDK8（及其旁系同源物 CDK19）的激酶活性部分通过磷酸化 HSF1-S326 促进 HSP70 表达并维持蛋白质稳态能力。这些结果表明 CKM 在保护细胞免受蛋白毒性应激方面发挥着重要作用。
Activated and promoter‐bound heat‐shock transcription factor 1 (HSF1) induces RNA polymerase II recruitment upon heat shock, and this is facilitated by the core Mediator inDrosophilaand yeast. Another Mediator module, CDK8 kinase module (CKM), consisting of four subunits including MED12 and CDK8, plays a negative or positive role in the regulation of transcription; however, its involvement in HSF1‐mediated transcription remains unclear. We herein demonstrated that HSF1 interacted with MED12 and recruited MED12 and CDK8 to theHSP70promoter during heat shock in mammalian cells. The kinase activity of CDK8 (and its paralog CDK19) promotedHSP70expression partly by phosphorylating HSF1‐S326 and maintained proteostasis capacity. These results indicate an important role for CKM in the protection of cells against proteotoxic stress.