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

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  • Chi Kwan Tsang

    (Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey
    Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey)

  • Yuan Liu

    (Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey
    The Graduate Program in Molecular and Cellular Pharmacology, Rutgers, the State University of New Jersey)

  • Janice Thomas

    (Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey
    Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey)

  • Yanjie Zhang

    (Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey
    Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey)

  • X. F. S. Zheng

    (Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey
    Robert Wood Johnson Medical School (RWJMS), 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.

Suggested Citation

  • Chi Kwan Tsang & Yuan Liu & Janice Thomas & Yanjie Zhang & X. F. S. Zheng, 2014. "Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4446
    DOI: 10.1038/ncomms4446
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