Inoue Toshiaki, Hiratsuka Masaharu, Osaki Mitsuhiko, Oshimura Mitsuo
Division of Human Genome Science, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Cell Cycle. 2007 May 2;6(9):1011-8. doi: 10.4161/cc.6.9.4219. Epub 2007 May 30.
Sir2, an NAD+-dependent protein deacetylase, extends the lifespan in diverse species from yeast to flies. Mammals have seven homologs of Sir2, SIRT1-7, which affect aging and metabolism and which are potential targets for pharmacologic intervention. We identified SIRT2, which preferentially deacetylates tubulin and histone H4, as a downregulated protein in gliomas due to its epigenetic aberration. We herein discuss the role of SIRT2 in the mitotic checkpoint function and show that it may be as a potential target of anti-cancer drugs.
Sir2是一种依赖烟酰胺腺嘌呤二核苷酸(NAD+)的蛋白质脱乙酰酶,可延长从酵母到果蝇等多种物种的寿命。哺乳动物有7种Sir2的同源物,即SIRT1 - 7,它们影响衰老和新陈代谢,是药物干预的潜在靶点。我们发现,由于其表观遗传异常,在胶质瘤中作为下调蛋白的SIRT2能优先使微管蛋白和组蛋白H4脱乙酰化。我们在此讨论SIRT2在有丝分裂检查点功能中的作用,并表明它可能是抗癌药物的潜在靶点。