Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction.
Cell
; 146(6): 969-79, 2011 Sep 16.
Article
em En
| MEDLINE
| ID: mdl-21906795
ABSTRACT
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 ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Transativadores
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Proteínas Serina-Treonina Quinases
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Proteínas de Saccharomyces cerevisiae
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Proteínas Quinases Ativadas por AMP
Idioma:
En
Revista:
Cell
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Taiwan