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Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5

Authors
 Soo-Yeon Park  ;  Jaesung Seo  ;  Hyo-Kyoung Choi  ;  Hye-Jeong Oh  ;  Garam Guk  ;  Yoo-Hyun Lee  ;  Jeongmin Lee  ;  Woo Jin Jun  ;  Kyung-Chul Choi  ;  Ho-Geun Yoon 
Citation
 SCIENTIFIC REPORTS, Vol.7 : 39222, 2017 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2017
Abstract
Programmed cell death 5 (PDCD5) is believed to play a crucial role in p53 activation; however, the underlying mechanism of how PDCD5 function is regulated during apoptosis remains obscure. Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser-119, which leads to PDCD5 destabilization. Overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, efficiently suppressed CK2α-mediated stabilization of PDCD5 and p53-mediated apoptosis in response to etoposide (ET). Conversely, PPEF-1 knockdown further enhanced genotoxic stress responses. Notably, PPEF-1 suppressed p53-mediated genotoxic stress response via negative regulation of PDCD5. We also determined that overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, significantly increased tumorigenic growth and chemoresistance of A549 human lung carcinoma cells. Collectively, these data demonstrate that PPEF-1 plays a pivotal role in tumorigenesis of lung cancer cells by reducing PDCD5-mediated genotoxic stress responses.
Files in This Item:
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DOI
10.1038/srep39222
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154093
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