PP2A-AMPK伪-HSF1 axis regulates the metal-inducible expression of HSPs and ROS clearance

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• 作者：Xiao-nian Zhu ; Li-ping Chen ; Qing Bai ; Lu Ma ; Dao-chuan Li ; Jin-miao Zhang ; Chen Gao ; Zi-ning Lei ; Zheng-bao Zhang ; Xiu-mei Xing ; Cai-xia Liu ; Zhi-ni He ; Jie Li ; Yong-mei Xiao ; Ai-hua Zhang ; Xiao-wen Zeng ; Wen Chen
• 关键词：ROS ; reactive oxygen species ; HSPs ; heat shock proteins ; PP2A ; protein phosphatase 2A ; AMPK伪 ; AMP-activated protein kinase 伪 subunit ; HSF1 ; heat shock transcription factor 1 ; NaAsO2 ; sodium arsenite ; CdCl2 ; cadmium chloride
• 刊名：Cellular Signalling
• 出版年：April, 2014
• 年：2014
• 卷：26
• 期：4
• 页码：825-832
• 全文大小：1244 K

文摘

Metals such as cadmium and arsenic are ubiquitous toxicants that cause a variety of adverse health effects. Heat shock proteins (HSPs) response to metal-induced stress and protect cells from further damage. However, the intracellular signalling pathways responsible for activation of HSPs expression are not fully understood. Here, we demonstrate that protein phosphatase 2A (PP2A) regulates expression of HSP70 and HSP27 via dephosphorylation of an AMP-activated protein kinase 伪 subunit (AMPK伪) at Thr172. Dephosphorylated AMPK伪 phosphorylates heat shock factor 1 (HSF1) at Ser303, leading to significant transcriptional suppression of HSP70 and HSP27 in CdCl₂- or NaAsO₂-treated cells. Suppression of PP2A regulatory B56未 subunit resulted in the sustained phosphorylation of AMPK伪 upon CdCl₂ treatment, subsequent reduction in expression of HSP70 and HSP27, and thereby dramatic reduction of reactive oxygen species (ROS) clearance. We further revealed that PP2A B56未 physically interacted with AMPK伪, providing evidence that PP2A B56未-AMPK伪-HSF1 signalling pathway participated in regulating the inducible expression of HSPs and ROS clearance. Taken together, we identified a novel PP2A-dependent signalling pathway involved in regulation of HSPs expression in response to metal stress.