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PLoS One. 2009 Dec 22;4(12):e8414. doi: 10.1371/journal.pone.0008414.

JNK1 phosphorylates SIRT1 and promotes its enzymatic activity.

Author information

  • 1Cardiovascular and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Incorporated, Cambridge, Massachusetts, USA.

Abstract

SIRT1 is a NAD-dependent deacetylase that regulates a variety of pathways including the stress protection pathway. SIRT1 deacetylates a number of protein substrates, including histones, FOXOs, PGC-1alpha, and p53, leading to cellular protection. We identified a functional interaction between cJUN N-terminal kinase (JNK1) and SIRT1 by coimmunoprecipitation of endogenous proteins. The interaction between JNK1 and SIRT1 was identified under conditions of oxidative stress and required activation of JNK1 via phosphorylation. Modulation of SIRT1 activity or protein levels using nicotinamide or RNAi did not modify JNK1 activity as measured by its ability to phosphorylate cJUN. In contrast, human SIRT1 was phosphorylated by JNK1 on three sites: Ser27, Ser47, and Thr530 and this phosphorylation of SIRT1 increased its nuclear localization and enzymatic activity. Surprisingly, JNK1 phosphorylation of SIRT1 showed substrate specificity resulting in deacetylation of histone H3, but not p53. These findings identify a mechanism for regulation of SIRT1 enzymatic activity in response to oxidative stress and shed new light on its role in the stress protection pathway.

PMID:
20027304
[PubMed - indexed for MEDLINE]
PMCID:
PMC2793009
Free PMC Article

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