Acetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction

被引：123

作者：

Lu, Jin-Ying ^{[7
,8
]}

Lin, Yu-Yi ^{[9
]}

Sheu, Jin-Chuan ^{[10
]}

Wu, June-Tai ^{[11
]}

Lee, Fang-Jen ^{[11
]}

Chen, Yue ^{[6
]}

Lin, Min-I ^{[7
]}

Chiang, Fu-Tien ^{[7
,10
]}

Tai, Tong-Yuan ^{[10
]}

Berger, Shelley L. ^{[5
]}

Zhao, Yingming ^{[6
]}

Tsai, Keh-Sung ^{[7
,8
,10
]}

Zhu, Heng ^{[1
,3
]}

Chuang, Lee-Ming ^{[8
,10
]}

Boeke, Jef D. ^{[2
,3
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD 21205 USA

[5] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA

[6] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA

[7] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Lab Med, Taipei 100, Taiwan

[8] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 100, Taiwan

[9] Natl Taiwan Univ, Coll Med, Inst Biochem & Mol Biol, Taipei 100, Taiwan

[10] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan

[11] Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan

来源：

CELL | 2011年 / 146卷 / 06期

关键词：

SNF1; PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; LIFE-SPAN; CAENORHABDITIS-ELEGANS; SCH9; SENESCENCE; EXTENSION; LONGEVITY; TARGET; STRESS;

D O I：

10.1016/j.cell.2011.07.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acetylation of histone and nonhistone proteins is an important posttranslational modification affecting many cellular processes. Here, we report that NuA4 acetylation of Sip2, a regulatory beta subunit of the Snf1 complex (yeast AMP-activated protein kinase), decreases as cells age. Sip2 acetylation, controlled by antagonizing NuA4 acetyltransferase and Rpd3 deacetylase, enhances interaction with Snf1, the catalytic subunit of Snf1 complex. Sip2-Snf1 interaction inhibits Snf1 activity, thus decreasing phosphorylation of a downstream target, Sch9 (homolog of Akt/S6K), and ultimately leading to slower growth but extended replicative life span. Sip2 acetylation mimetics are more resistant to oxidative stress. We further demonstrate that the anti-aging effect of Sip2 acetylation is independent of extrinsic nutrient availability and TORC1 activity. We propose a protein acetylation-phosphorylation cascade that regulates Sch9 activity, controls intrinsic aging, and extends replicative life span in yeast.

引用

页码：968 / 978

页数：11

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