Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep39222
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015R1D1A4A01016406]
- NRF grant - Korea Government (MSIP) [NRF-2015R1A2A1A05000899, NRF-2011-0030086, NRF-2015R1A2A1A15056063]
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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-1(D172)N, efficiently suppressed CK2 alpha-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-1(D172N), 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.
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