沉默调节蛋白1如何影响新陈代谢、衰老和癌症？
How does SIRT1 affect metabolism, senescence and cancer?
作者信息
Brooks Christopher L, Gu Wei
机构信息
Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.
出版信息
Nat Rev Cancer. 2009 Feb;9(2):123-8. doi: 10.1038/nrc2562. Epub 2008 Dec 29.
Abstract
SIRT1 is a multifaceted, NAD(+)-dependent protein deacetylase that is involved in a wide variety of cellular processes from cancer to ageing. The function of SIRT1 in cancer is complex: SIRT1 has been shown to have oncogenic properties by downregulating p53 activity, but recent studies indicate that SIRT1 acts as a tumour suppressor in a mutated p53 background, raising intriguing questions regarding its mechanism of action. Here we discuss the current understanding of how SIRT1 functions in light of recent discoveries and propose that the net outcome of the seemingly opposite oncogenic and tumour-suppressive effects of SIRT1 depends on the status of p53.
摘要
沉默调节蛋白1（SIRT1）是一种多功能的、依赖烟酰胺腺嘌呤二核苷酸（NAD⁺）的蛋白质脱乙酰酶，参与从癌症到衰老等各种各样的细胞过程。SIRT1在癌症中的功能很复杂：已表明SIRT1通过下调p53活性具有致癌特性，但最近的研究表明，在p53发生突变的背景下，SIRT1发挥肿瘤抑制因子的作用，这就引发了关于其作用机制的有趣问题。在此，我们根据最近的发现讨论目前对SIRT1功能的理解，并提出SIRT1看似相反的致癌和肿瘤抑制作用的最终结果取决于p53的状态。
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