Yi Jingjie, Luo Jianyuan
Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Biochim Biophys Acta. 2010 Aug;1804(8):1684-9. doi: 10.1016/j.bbapap.2010.05.002. Epub 2010 May 13.
NAD(+)-dependent Class III histone deacetylase SIRT1 is a multiple function protein critically involved in stress responses, cellular metabolism and aging through deacetylating a variety of substrates including p53, forkhead-box transcription factors, PGC-1alpha, NF-kappaB, Ku70 and histones. The first discovered non-histone target of SIRT1, p53, is suggested to play a central role in SIRT1-mediated functions in tumorigenesis and senescence. SIRT1 was originally considered to be a potential tumor promoter since it negatively regulates the tumor suppressor p53 and other tumor suppressors. There is new evidence that SIRT1 acts as a tumor suppressor based on its role in negatively regulating beta-catenin and survivin. This review provides an overview of current knowledge of SIRT1-p53 signaling and controversies regarding the functions of SIRT1 in tumorigenesis.
烟酰胺腺嘌呤二核苷酸（NAD⁺）依赖性Ⅲ类组蛋白去乙酰化酶SIRT1是一种多功能蛋白，通过使包括p53、叉头框转录因子、PGC-1α、核因子κB、Ku70和组蛋白在内的多种底物去乙酰化，在应激反应、细胞代谢和衰老过程中发挥关键作用。SIRT1首个被发现的非组蛋白靶点p53，被认为在SIRT1介导的肿瘤发生和衰老功能中起核心作用。SIRT1最初被认为是一种潜在的肿瘤促进因子，因为它对肿瘤抑制因子p53和其他肿瘤抑制因子起负调控作用。基于其对β-连环蛋白和生存素的负调控作用，有新证据表明SIRT1可作为肿瘤抑制因子。本文综述了目前关于SIRT1-p53信号传导的知识以及SIRT1在肿瘤发生中功能的争议。
