Peptide Switch Is Essential for Sirt1 Deacetylase Activity
作者: Hyeog KangJeong-Yong SuhYoung-Sang JungJae-Won JungMyung K. KimJay H. Chung
作者单位: 1Laboratory of Obesity and Aging Research, Genetics and Development Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Gwanak-gu, Seoul 151-921, Korea
3Korea Basic Science Institute, Seoul 136-701, Korea
刊名: Molecular Cell, 2011, Vol.44 (2), pp.203-213
来源数据库: Elsevier Journal
DOI: 10.1016/j.molcel.2011.07.038
原始语种摘要: Summary(#br)In mammals, the Sirtuins are composed of seven Sir2 orthologs (Sirt1 – 7) with a conserved deacetylase core that utilizes NAD + as a cofactor. Interestingly, the deacetylase core of Sirt1 by itself has no catalytic activity. We found within the C-terminal domain a 25 aa sequence that is essential for Sirt1 activity (ESA). Our results indicate that the ESA region interacts with and functions as an “on switch” for the deacetylase core. The endogenous Sirt1 inhibitor DBC1, which also binds to the deacetylase core, competes with and inhibits the ESA region from interacting with the deacetylase core. We discovered an ESA mutant peptide that can bind to the deacetylase core and inhibit Sirt1 in trans . By using this mutant peptide, we were able to inhibit Sirt1 activity and to...
全文获取路径: Elsevier  (合作)
影响因子:15.28 (2012)