The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status.
The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status.
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DOI：
10.1038/srep00640
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发表时间：
2012
影响因子：
4.6
通讯作者：
Li, Xiaoling
中科院分区：
文献类型：
--
作者：
Guo, Xiumei;Kesimer, Mehmet;Tolun, Goekhan;Zheng, Xunhai;Xu, Qing;Lu, Jing;Sheehan, John K.;Griffith, Jack D.;Li, Xiaoling
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 Thr522 residue in response to environmental stress. Here we demonstrate that phosphorylation of Thr522 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.
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DOI：
10.1073/pnas.0801613105
发表时间：
2008-09-09
影响因子：
11.1
作者：
Yamakuchi, Munekazu;Ferlito, Marcella;Lowenstein, Charles J.
通讯作者：
Lowenstein, Charles J.
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1083/jcb.200205057
发表时间：
2002-08-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Schwer B;North BJ;Frye RA;Ott M;Verdin E
通讯作者：
Verdin E
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
64.5
作者：
Nakahata Y;Kaluzova M;Grimaldi B;Sahar S;Hirayama J;Chen D;Guarente LP;Sassone-Corsi P
通讯作者：
Sassone-Corsi P