title: Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction.
abstract: We previously reported that Polo-like kinase 2 (PLK2) is highly expressed in cells with defective mitochondrial respiration and is essential for their survival. Although PLK2 has been widely studied as a cell cycle regulator, we have uncovered an antioxidant function for this kinase that activates the GSK3-NRF2 signaling pathway. Here, we report that the expression of PLK2 is responsive to oxidative stress and that PLK2 mediates antioxidant signaling by phosphorylating GSK3, thereby promoting the nuclear translocation of NRF2. We further show that the antioxidant activity of PLK2 is essential for preventing p53-dependent necrotic cell death. Thus, the regulation of redox homeostasis by PLK2 promotes the survival of cells with dysfunctional mitochondria, which may have therapeutic implications for cancer and neurodegenerative diseases.
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; State Key Laboratory for Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ma
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ping-yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Hurley
authors.affiliation: Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Bunz
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: hwangp@mail.nih.gov.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hwang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014183:Transplantation, Heterologous
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3
keywords: Antioxidant; Free radicals; GSK3; Mitochondrial dysfunction; NRF2; Necrosis; Oxidative stress; Polo-like kinase 2; p53