title: Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance.
abstract: Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signalling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization.
authors.affiliation: 1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] Department of Pharmacology, Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
authors.forename: Chi Kwan
authors.initials: CK
authors.lastname: Tsang
authors.affiliation: 1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] The Graduate Program in Molecular and Cellular Pharmacology, Rutgers, the State University of New Jersey.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] Department of Pharmacology, Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Thomas
authors.affiliation: 1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] Department of Pharmacology, Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] Department of Pharmacology, Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
authors.forename: X F S
authors.initials: XF
authors.lastname: Zheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C104169:DUN1 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases