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

Authors

Xiumei Guo, United States National Institute of Environmental Health Sciences
Mehmet Kesimer, University of North Carolina at Chapel Hill
Gökhan Tolun, University of North Carolina at Chapel HillFollow
Xunhai Zheng, United States National Institute of Environmental Health Sciences
Qing Xu, United States National Institute of Environmental Health Sciences
Jing Lu, United States National Institute of Environmental Health Sciences
John K. Sheehan, University of North Carolina at Chapel Hill
Jack D. Griffith, University of North Carolina
Xiaoling Li, United States National Institute of Environmental Health Sciences

RIS ID

129310

Publication Details

Guo, X., Kesimer, M., Tolun, G., Zheng, X., Xu, Q., Lu, J., Sheehan, J. K., Griffith, J. & Li, X. (2012). The NAD⁺-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status. Scientific Reports, 2 640--640-.

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.