Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

Chi Kwan Tsang; Yuan Liu; Janice Thomas; Yanjie Zhang; X F S Zheng

doi:10.1038/ncomms4446

Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

Nat Commun. 2014 Mar 19:5:3446. doi: 10.1038/ncomms4446.

Authors

Chi Kwan Tsang¹, Yuan Liu², Janice Thomas¹, Yanjie Zhang¹, X F S Zheng¹

Affiliations

¹ 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.
² 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.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Active Transport, Cell Nucleus
Blotting, Western
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Nucleus / metabolism*
Fibroblasts / cytology
Fibroblasts / enzymology
Fibroblasts / metabolism
Gene Expression Regulation, Fungal / drug effects
Humans
Hydrogen Peroxide / pharmacology
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Microscopy, Fluorescence
Mutation
Oligonucleotide Array Sequence Analysis
Oxidants / pharmacology
Oxidative Stress*
Phosphorylation
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae / enzymology
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism*
Superoxide Dismutase-1
Superoxides / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptome / drug effects
Transcriptome / genetics

Substances

Cell Cycle Proteins
Intracellular Signaling Peptides and Proteins
Oxidants
Reactive Oxygen Species
SOD1 protein, human
Saccharomyces cerevisiae Proteins
Transcription Factors
Superoxides
Hydrogen Peroxide
Superoxide Dismutase
Superoxide Dismutase-1
DUN1 protein, S cerevisiae
MEC1 protein, S cerevisiae
Protein Serine-Threonine Kinases

Associated data

GEO/GSE55081

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding