HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth.

Authors

Kuo-Hui Su, The Jackson LaboratoryFollow
Junyue Cao, The Jackson LaboratoryFollow
Zijian Tang, The Jackson LaboratoryFollow
Siyuan Dai, The Jackson LaboratoryFollow
Yishu He, The Jackson LaboratoryFollow
Stephen B. Sampson, The Jackson LaboratoryFollow
Ivor J Benjamin
Chengkai Dai, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

5-2016

JAX Source

Nat Cell Biol 2016 May; 18(5):527-39

Volume

18

Issue

5

First Page

527

Last Page

539

ISSN

1476-4679

PMID

27043084

Grant

CA034196, 1DP2OD007070, AS-NS-0599-09

Abstract

To cope with proteotoxic stress, cells attenuate protein synthesis. However, the precise mechanisms underlying this fundamental adaptation remain poorly defined. Here we report that mTORC1 acts as an immediate cellular sensor of proteotoxic stress. Surprisingly, the multifaceted stress-responsive kinase JNK constitutively associates with mTORC1 under normal growth conditions. On activation by proteotoxic stress, JNK phosphorylates both RAPTOR at S863 and mTOR at S567, causing partial disintegration of mTORC1 and subsequent translation inhibition. Importantly, HSF1, the central player in the proteotoxic stress response (PSR), preserves mTORC1 integrity and function by inactivating JNK, independently of its canonical transcriptional action. Thereby, HSF1 translationally augments the PSR. Beyond promoting stress resistance, this intricate HSF1-JNK-mTORC1 interplay, strikingly, regulates cell, organ and body sizes. Thus, these results illuminate a unifying mechanism that controls stress adaptation and growth. Nat Cell Biol 2016 May; 18(5):527-39

Recommended Citation

Su K, Cao J, Tang Z, Dai S, He Y, Sampson SB, Benjamin I, Dai C. HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth. Nat Cell Biol 2016 May; 18(5):527-39