2. Academic Validation
  3. Heat stress activates YAP/TAZ to induce the heat shock transcriptome

Heat stress activates YAP/TAZ to induce the heat shock transcriptome

  • Nat Cell Biol. 2020 Dec;22(12):1447-1459. doi: 10.1038/s41556-020-00602-9.
Min Luo 1 2 3,  Zhipeng Meng 3 4,  Toshiro Moroishi 5 6 7,  Kimberly C Lin 3,  Guobo Shen 1,  Fei Mo 1,  Bin Shao 2,  Xiawei Wei 1,  Ping Zhang 2,  Yuquan Wei 1,  Kun-Liang Guan 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 2 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
  • 4 Department of Molecular and Cellular Pharmacology & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
  • 5 Department of Cell Signaling and Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • 6 Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • 7 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Saitama, Japan.
  • 8 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. kuguan@health.ucsd.edu.
PMID: 33199845 DOI: 10.1038/s41556-020-00602-9
Abstract

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.

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