title: The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status.
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 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.
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, ResearchTriangle Park, NC 27709, USA.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Guo
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kesimer
authors.forename: Gökhan
authors.initials: G
authors.lastname: Tolun
authors.forename: Xunhai
authors.initials: X
authors.lastname: Zheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: John K
authors.initials: JK
authors.lastname: Sheehan
authors.forename: Jack D
authors.initials: JD
authors.lastname: Griffith
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002470:Cell Survival; D004789:Enzyme Activation; D057809:HEK293 Cells; D018869:Heat-Shock Response; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D056564:Sirtuin 1 / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D016159:Tumor Suppressor Protein p53; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1