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

Chi K.wan 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

Chi K.wan Tsang, Yuan Liu, Janice Thomas, Yanjie Zhang, X. F.S. Zheng

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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.

Original language	English (US)
Article number	3446
Pages (from-to)	3446
Number of pages	1
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4446
State	Published - 2014

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{0029801340324dfb94a3279fe0c5f801,

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. ",

author = "Tsang, {Chi K.wan} and Yuan Liu and Janice Thomas and Yanjie Zhang and Zheng, {X. F.S.}",

note = "Funding Information: We thank Michael Moreau for DNA microarray analysis, Miao Chen and Lisa Lyu for technical assistance and reagents, and Val Culotta and Phil Furmanski for helpful discussions. This work was supported by NIH grants R01 CA123391.",

year = "2014",

doi = "10.1038/ncomms4446",

language = "English (US)",

volume = "5",

pages = "3446",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

AU - Tsang, Chi K.wan

AU - Liu, Yuan

AU - Thomas, Janice

AU - Zhang, Yanjie

AU - Zheng, X. F.S.

N1 - Funding Information: We thank Michael Moreau for DNA microarray analysis, Miao Chen and Lisa Lyu for technical assistance and reagents, and Val Culotta and Phil Furmanski for helpful discussions. This work was supported by NIH grants R01 CA123391.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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

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