PMID- 21909427 OWN - NLM STAT- MEDLINE DCOM- 20120105 LR - 20211203 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 9 DP - 2011 TI - PP1A-mediated dephosphorylation positively regulates YAP2 activity. PG - e24288 LID - 10.1371/journal.pone.0024288 [doi] LID - e24288 AB - 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. FAU - Wang, Pei AU - Wang P AD - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. FAU - Bai, Yujie AU - Bai Y FAU - Song, Bangrong AU - Song B FAU - Wang, Yadong AU - Wang Y FAU - Liu, Dong AU - Liu D FAU - Lai, Yongqiang AU - Lai Y FAU - Bi, Xiaolin AU - Bi X FAU - Yuan, Zengqiang AU - Yuan Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110901 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Phosphoproteins) RN - 0 (Transcription Factors) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) RN - EC 3.1.3.16 (PPP1CA protein, human) RN - EC 3.1.3.16 (Protein Phosphatase 1) SB - IM MH - Adaptor Proteins, Signal Transducing/*metabolism MH - Cell Line, Tumor MH - Cell Nucleus/metabolism MH - Cell Survival MH - Humans MH - Phosphoproteins/*metabolism MH - Phosphorylation MH - Protein Binding MH - Protein Phosphatase 1/*metabolism MH - Transcription Factors MH - Transcription, Genetic MH - Transcriptional Activation/genetics MH - YAP-Signaling Proteins PMC - PMC3164728 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/09/13 06:00 MHDA- 2012/01/06 06:00 PMCR- 2011/09/01 CRDT- 2011/09/13 06:00 PHST- 2011/07/11 00:00 [received] PHST- 2011/08/03 00:00 [accepted] PHST- 2011/09/13 06:00 [entrez] PHST- 2011/09/13 06:00 [pubmed] PHST- 2012/01/06 06:00 [medline] PHST- 2011/09/01 00:00 [pmc-release] AID - PONE-D-11-13141 [pii] AID - 10.1371/journal.pone.0024288 [doi] PST - ppublish SO - PLoS One. 2011;6(9):e24288. doi: 10.1371/journal.pone.0024288. Epub 2011 Sep 1.