Heat stress activates YAP/TAZ to induce the heat shock transcriptome.
Heat stress activates YAP/TAZ to induce the heat shock transcriptome.
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热应激激活YAP/TAZ诱导热休克转录组
DOI：
10.1038/s41556-020-00602-9
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发表时间：
2020-12
影响因子：
21.3
通讯作者：
Guan KL
中科院分区：
文献类型：
--
作者：
Luo M;Meng Z;Moroishi T;Lin KC;Shen G;Mo F;Shao B;Wei X;Zhang P;Wei Y;Guan KL
Hippo通路在细胞生长、分化、器官发育和组织稳态中起关键作用，而其失调可导致肿瘤发生。雅普/TAZ是转录共激活因子，代表Hippo途径的主要下游效应子。在这里，我们表明，热应激诱导强烈和快速的雅普去磷酸化和激活。热休克对雅普的影响对已知调节Hippo通路的其他信号是显性的。热休克通过促进HSP 90依赖的LATS与PP 5磷酸酶的相互作用和PP 5磷酸酶的失活来抑制LATS激酶。热休克还诱导LATS泛素化和降解。雅普/TAZ对细胞热休克反应，包括热休克转录组和细胞活力至关重要。本研究揭示了Hippo对热休克的调控机制以及雅普在热应激反应中的生理功能。我们的观察结果还揭示了一种潜在的联合治疗，涉及高热和靶向Hippo通路。
The Hippo pathway plays critical roles in cell growth, differentiation, organ development, and tissue homeostasis whereas its dysregulation can lead to tumorigenesis. YAP/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 PP5 phosphatase. Heat shock also induces LATS ubiquitination and degradation. YAP/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 heat stress response. Our observations also reveal a potential combinational therapy involving hyperthermia and targeting of the Hippo pathway.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
影响因子：
16.6
作者：
Meng Z;Moroishi T;Mottier-Pavie V;Plouffe SW;Hansen CG;Hong AW;Park HW;Mo JS;Lu W;Lu S;Flores F;Yu FX;Halder G;Guan KL
通讯作者：
Guan KL
影响因子：
5.3
作者：
Budzynski, Marek A.;Puustinen, Mikael C.;Sistonen, Lea
通讯作者：
Sistonen, Lea
DOI：
10.1073/pnas.1101273108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Ho, King Ching;Zhou, Zhonghua;Yang, Xiaolong
通讯作者：
Yang, Xiaolong
DOI：
10.1146/annurev-cancerbio-030617-050202
发表时间：
2018-01-01
期刊：
ANNUAL REVIEW OF CANCER BIOLOGY, VOL 2
影响因子：
--
作者：
Lin, Kimberly C.;Park, Hyun Woo;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang