SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria

被引：447
作者：
Onyango, P
Celic, I
McCaffery, JM
Boeke, JD
Feinberg, AP
机构：
[1] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Biol, Integrated Imaging ctr, Baltimore, MD 21218 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 21期
关键词：
D O I：
10.1073/pnas.222538099
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 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.
引用
收藏
页码：13653 / 13658
页数：6
相关论文
共 32 条
[21]   A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast [J].
Perrod, S ;
Cockell, MM ;
Laroche, T ;
Renauld, H ;
Ducrest, AL ;
Bonnard, C ;
Gasser, SM .
EMBO JOURNAL, 2001, 20 (1-2) :197-209
[22]   Pch2 links chromatin silencing to meiotic checkpoint control [J].
San-Segundo, PA ;
Roeder, GS .
CELL, 1999, 97 (03) :313-324
[23]   The conserved core of a human SIR2 homologue functions in yeast silencing [J].
Sherman, JM ;
Stone, EM ;
Freeman-Cook, LL ;
Brachmann, CB ;
Boeke, JD ;
Pillus, L .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (09) :3045-3059
[24]   A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family [J].
Smith, JS ;
Brachmann, CB ;
Celic, I ;
Kenna, MA ;
Muhammad, S ;
Starai, VJ ;
Avalos, JL ;
Escalante-Semerena, JC ;
Grubmeyer, C ;
Wolberger, C ;
Boeke, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6658-6663
[25]   An unusual form of transcriptional silencing in yeast ribosomal DNA [J].
Smith, JS ;
Boeke, JD .
GENES & DEVELOPMENT, 1997, 11 (02) :241-254
[26]   Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity [J].
Straight, AF ;
Shou, WY ;
Dowd, GJ ;
Turck, CW ;
Deshaies, RJ ;
Johnson, AD ;
Moazed, D .
CELL, 1999, 97 (02) :245-256
[27]   An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing [J].
Tanny, JC ;
Dowd, GJ ;
Huang, J ;
Hilz, H ;
Moazed, D .
CELL, 1999, 99 (07) :735-745
[28]   Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans [J].
Tissenbaum, HA ;
Guarente, L .
NATURE, 2001, 410 (6825) :227-230
[29]   CobB, a new member of the SIR2 family of eucaryotic regulatory proteins, is required to compensate for the lack of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants during cobalamin biosynthesis in Salmonella typhimurium LT2 [J].
Tsang, AW ;
Escalante-Semerena, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (48) :31788-31794
[30]   Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae [J].
Tsukamoto, Y ;
Kato, J ;
Ikeda, H .
NATURE, 1997, 388 (6645) :900-903
1234