DBC1 is a negative regulator of SIRT1

被引：419
作者：
Kim, Ja-Eun [1 ]
Chen, Junjie [1 ]
Lou, Zhenkun [2 ]
机构：
[1] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA
[2] Mayo Clin, Coll Med, Div Oncol Res, Rochester, MN 55905 USA
来源：
NATURE | 2008年 / 451卷 / 7178期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1038/nature06500
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The NAD- dependent protein deacetylase Sir2 ( silent information regulator 2) regulates lifespan in several organisms(1-3). SIRT1, the mammalian orthologue of yeast Sir2, participates in various cellular functions(4-7) and possibly tumorigenesis(8). Whereas the cellular functions of SIRT1 have been extensively investigated, less is known about the regulation of SIRT1 activity. Here we show that Deleted in Breast Cancer- 1 ( DBC1), initially cloned from a region ( 8p21) homozygously deleted in breast cancers(9), forms a stable complex with SIRT1. DBC1 directly interacts with SIRT1 and inhibits SIRT1 activity in vitro and in vivo. Downregulation of DBC1 expression potentiates SIRT1- dependent inhibition of apoptosis induced by genotoxic stress. Our results shed new light on the regulation of SIRT1 and have important implications in understanding the molecular mechanism of ageing and cancer.
引用
收藏
页码：583 / U10
页数：5
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