title: Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jaesung
authors.initials: J
authors.lastname: Seo
authors.affiliation: Division of Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do, South Korea.
authors.forename: Hyo-Kyoung
authors.initials: HK
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Garam
authors.initials: G
authors.lastname: Guk
authors.affiliation: Department of Food and Nutrition, The University of Suwon, Kyunggi-do 445-743, South Korea.
authors.forename: Yoo-Hyun
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Medical Nutrition, Kyung Hee University, Kyunggi-do, 446-701, South Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Chonnam National University, Gwangju, South Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Jun
authors.affiliation: Department of Biomedical Sciences, and Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
mesh_terms: D000072283:A549 Cells; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism; D049109:Cell Proliferation; D004249:DNA Damage; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II; C107424:PPEF1 protein, human; D010749:Phosphoprotein Phosphatases