한빛사논문
- 조회2,974
Abstract
Hyeog Kang,1 Jeong-Yong Suh,2 Young-Sang Jung,3 Jae-Won Jung,1 Myung K. Kim,1 and Jay H. Chung1,*
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
*Correspondence: Jay H. Chung
Summary
In mammals, the Sirtuins are composed of seven Sir2 orthologs (Sirt17) 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 increase the chemosensitivity of androgen-refractory prostate cancer cells. Therefore, the ESA region is a potential target for development of therapies to regulate Sirt1.
논문정보
- Research article
- 2011년 10월 (BRIC 등록일 )
- 국내+국외 연구진
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