SIRT3是一种人类SIR2同源物，是一种定位于线粒体的NAD依赖性脱乙酰酶。
SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria.
作者信息
Onyango Patrick, Celic Ivana, McCaffery J Michael, Boeke Jef D, Feinberg Andrew P
机构信息
Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8. doi: 10.1073/pnas.222538099. Epub 2002 Oct 8.
Abstract
The SIR2 (silent information regulator 2) gene family has diverse functions in yeast including gene silencing, DNA repair, cell-cycle progression, and chromosome fidelity in meiosis and aging. Human homologues, termed sirtuins, are highly conserved but are of unknown function. We previously identified a large imprinted gene domain on 11p15.5 and investigated the 11p15.5 sirtuin SIRT3. Although this gene was not imprinted, we found that it is localized to mitochondria, with a mitochondrial targeting signal within a unique N-terminal peptide sequence. The encoded protein was found also to possess NAD(+)-dependent histone deacetylase activity. These results suggest a previously unrecognized organelle for sirtuin function and that the role of SIRT3 in mitochondria involves protein deacetylation.
摘要
SIR2（沉默信息调节因子2）基因家族在酵母中具有多种功能，包括基因沉默、DNA修复、细胞周期进程以及减数分裂和衰老过程中的染色体保真度。其人类同源物称为沉默调节蛋白，高度保守但功能未知。我们之前在11p15.5上鉴定出一个大的印记基因结构域，并对11p15.5沉默调节蛋白SIRT3进行了研究。尽管该基因没有印记，但我们发现它定位于线粒体，在一个独特的N端肽序列内有一个线粒体靶向信号。还发现编码的蛋白质具有NAD(+)依赖性组蛋白脱乙酰酶活性。这些结果表明沉默调节蛋白功能存在一个以前未被认识的细胞器，并且SIRT3在线粒体中的作用涉及蛋白质去乙酰化。
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1
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Cell. 2001 Oct 19;107(2):149-59. doi: 10.1016/s0092-8674(01)00527-x.
2
Negative control of p53 by Sir2alpha promotes cell survival under stress.Sir2α 对 p53 的负调控在应激条件下促进细胞存活。
Cell. 2001 Oct 19;107(2):137-48. doi: 10.1016/s0092-8674(01)00524-4.
3
Deciphering NAD-dependent deacetylases.解析NAD依赖的脱乙酰酶
Cell. 2001 Apr 20;105(2):161-4. doi: 10.1016/s0092-8674(01)00305-1.
4
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EMBO J. 2001 Mar 15;20(6):1353-62. doi: 10.1093/emboj/20.6.1353.
5
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans.增加sir-2基因的剂量可延长秀丽隐杆线虫的寿命。
Nature. 2001 Mar 8;410(6825):227-30. doi: 10.1038/35065638.
6
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EMBO J. 2001 Jan 15;20(1-2):197-209. doi: 10.1093/emboj/20.1.197.
7
A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.Sir2蛋白家族中一种系统发育保守的NAD⁺依赖性蛋白脱乙酰酶活性。
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9
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