The NAD +-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status

Xiumei Guo, Mehmet Kesimer, Gã Tolun, Xunhai Zheng, Qing Xu, Jing Lu, John K. Sheehan, Jack D. Griffith, Xiaoling Li

Research output: Contribution to journalArticle

Abstract

SIRT1, a NAD +-dependent protein deacetylase, is an important regulator in cellular stress response and energy metabolism. While the list of SIRT1 substrates is growing, how the activity of SIRT1 is regulated remains unclear. We have previously reported that SIRT1 is activated by phosphorylation at a conserved Thr 522 residue in response to environmental stress. Here we demonstrate that phosphorylation of Thr 522 activates SIRT1 through modulation of its oligomeric status. We provide evidence that nonphosphorylated SIRT1 protein is aggregation-prone in vitro and in cultured cells. Conversely, phosphorylated SIRT1 protein is largely in the monomeric state and more active. Our findings reveal a novel mechanism for environmental regulation of SIRT1 activity, which may have important implications in understanding the molecular mechanism of stress response, cell survival, and aging.

Original languageEnglish (US)
Article number00640
JournalScientific Reports
Volume2
DOIs
StatePublished - 2012
Externally publishedYes

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NAD
Phosphorylation
Proteins
Cell Aging
Energy Metabolism
Cultured Cells
Cell Survival
In Vitro Techniques

ASJC Scopus subject areas

  • General

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The NAD +-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status. / Guo, Xiumei; Kesimer, Mehmet; Tolun, Gã; Zheng, Xunhai; Xu, Qing; Lu, Jing; Sheehan, John K.; Griffith, Jack D.; Li, Xiaoling.

In: Scientific Reports, Vol. 2, 00640, 2012.

Research output: Contribution to journalArticle

Guo, X, Kesimer, M, Tolun, G, Zheng, X, Xu, Q, Lu, J, Sheehan, JK, Griffith, JD & Li, X 2012, 'The NAD +-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status', Scientific Reports, vol. 2, 00640. https://doi.org/10.1038/srep00640
Guo, Xiumei ; Kesimer, Mehmet ; Tolun, Gã ; Zheng, Xunhai ; Xu, Qing ; Lu, Jing ; Sheehan, John K. ; Griffith, Jack D. ; Li, Xiaoling. / The NAD +-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status. In: Scientific Reports. 2012 ; Vol. 2.
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AU - Xu, Qing

AU - Lu, Jing

AU - Sheehan, John K.

AU - Griffith, Jack D.

AU - Li, Xiaoling

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