Open AccessHeat stress activates YAP/TAZ to induce the heat shock transcriptome
Author(s) -
Min Luo,
Zhipeng Meng,
Toshiro Moroishi,
Kai Lin,
Guobo Shen,
Fei Mo,
Bin Shao,
Xiawei Wei,
Ping Zhang,
Yuquan Wei,
KunLiang Guan
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-00602-9
Subject(s) - microbiology and biotechnology , hippo signaling pathway , heat shock protein , heat shock , dephosphorylation , heat shock factor , biology , hsf1 , transcription factor , transcriptome , signal transduction , chemistry , phosphorylation , phosphatase , hsp70 , biochemistry , gene expression , gene
The Hippo pathway plays critical roles in cell growth, differentiation, organ development and tissue homeostasis, whereas its dysregulation can lead to tumorigenesis. YAP and TAZ are transcription co-activators and represent the main downstream effectors of the Hippo pathway. Here, we show that heat stress induces a strong and rapid YAP dephosphorylation and activation. The effect of heat shock on YAP is dominant to other signals known to modulate the Hippo pathway. Heat shock inhibits LATS kinase by promoting HSP90-dependent LATS interaction with and inactivation by protein phosphatase 5. Heat shock also induces LATS ubiquitination and degradation. YAP and TAZ are crucial for cellular heat shock responses, including the heat shock transcriptome and cell viability. This study uncovers previously unknown mechanisms of Hippo regulation by heat shock, as well as physiological functions of YAP, in the heat stress response. Our observations also reveal a potential combinational therapy involving hyperthermia and targeting of the Hippo pathway.