Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction |
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| Affiliation: | 1. Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA;2. State Key Laboratory for Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China;3. Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA;4. Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA;1. Shanghai Key Laboratory of Data Science, School of Computer Science, Fudan University, Shanghai, China;2. School of Information Systems, Singapore Management University, Singapore;3. Computer Science and Engineering Department, University of North Texas, USA;1. Department of Chemical and Biomolecular Engineering, New York University, 6 MetroTech Center, Brooklyn, NY, 11201, USA;2. Department of Biomedical Engineering, New York University, 6 MetroTech Center, Brooklyn, NY, 11201, USA;3. Department of Chemistry, New York City College of Technology, 300 Jay St, Brooklyn, NY, 11201, USA |
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| 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. |
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| Keywords: | Polo-like kinase 2 Antioxidant Mitochondrial dysfunction Oxidative stress GSK3 NRF2 p53 Necrosis Free radicals |
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