Premium
MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells
Author(s) -
Srivastava Pratibha,
Takii Ryosuke,
Okada Mariko,
Fujimoto Mitsuaki,
Nakai Akira
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14139
Subject(s) - hsf1 , heat shock factor , heat shock , microbiology and biotechnology , proteostasis , transcription (linguistics) , biology , mediator , promoter , transcription factor , hsp70 , rna polymerase ii , heat shock protein , genetics , gene , gene expression , linguistics , philosophy
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 in Drosophila and 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 the HSP70 promoter during heat shock in mammalian cells. The kinase activity of CDK8 (and its paralog CDK19) promoted HSP70 expression 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.