PP1A-Mediated Dephosphorylation Positively Regulates YAP2 Activity

PLoS One

Yujie Bai¹  Yadong Wang¹  Xiaolin Bi¹  Zengqiang Yuan²  Dong Liu²  Pei Wang³  Yongqiang Lai³  Bangrong Song³ 

[1] College of Life Sciences, Graduate School of the Chinese Academy of Sciences, Beijing, China;Department of Cardiac Surgery, Anzhen Hospital at Capital Medical University, Beijing, China;State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

关键词: HeLa cells;    Immunoprecipitation;    Phosphorylation;    Serine;    Cell death;    Recombinant proteins;    In vitro kinase assay;    Ovarian cancer;   

DOI  :  10.1371/journal.pone.0024288

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background The Hippo/MST1 signaling pathway plays an important role in the regulation of cell proliferation and apoptosis. As a major downstream target of the Hippo/MST1 pathway, YAP2 (Yes-associated protein 2) functions as a transcriptional cofactor that has been implicated in many biological processes, including organ size control and cancer development. MST1/Lats kinase inhibits YAP2's nuclear accumulation and transcriptional activity through inducing the phosphorylation at serine 127 and the sequential association with 14-3-3 proteins. However, the dephosphorylation of YAP2 is not fully appreciated. Methodology/Principal Findings In the present study, we demonstrate that PP1A (catalytic subunit of protein phosphatase-1) interacts with and dephosphorylates YAP2 in vitro and in vivo, and PP1A-mediated dephosphorylation induces the nuclear accumulation and transcriptional activation of YAP2. Inhibition of PP1 by okadiac acid (OA) increases the phosphorylation at serine 127 and cytoplasmic translocation of YAP2 proteins, thereby mitigating its transcription activity. PP1A expression enhances YAP2's pro-survival capability and YAP2 knockdown sensitizes ovarian cancer cells to cisplatin treatment. Conclusions/Significance Our findings define a novel molecular mechanism that YAP2 is positively regulated by PP1-mediated dephosphorylation in the cell survival.

【 授权许可】

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