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JNK2 dependent regulation of SIRT1 protein stability

Ford, J, Ahmed, Shafiq, Allison, S, Jiang, M and Milner, J (2008) JNK2 dependent regulation of SIRT1 protein stability. Cell Cycle, 7 (19). pp. 3091-3097.

Item Type: Article

Abstract

Mammalian SIRT1 is an NAD-dependent deacetylase with critical roles in the maintenance of homeostasis and cell survival. Elevated levels of SIRT1 protein are evident in cancer in which SIRT1 can function as a cancer-specific survival factor. Here we demonstrate that elevated SIRT1 protein in human cells is not attributable to increased SIRT1 mRNA levels but, instead, reflects SIRT1 protein stability. RNAi-mediated depletion of JNK2 reduced the half-life of SIRT1 protein from >9 h to <2 h and this correlated with lack of SIRT1 protein phosphorylation at serine 27. In contrast, depletion of JNK1 had no effect upon SIRT1 protein stability and SIRT1 phosphorylation at serine 47 showed no correlation with SIRT1 protein stability. Thus we show that JNK2 is linked, directly or indirectly, with SIRT1 protein stability and that this function is coupled with SIRT1 phosphorylation at serine 27. Our observations identify a route for therapeutic modulation of SIRT1 protein levels in SIRT1-linked diseases including cancer, neurodegeneration and diabetes.

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More Information

Depositing User: Paula Normington

Identifiers

Item ID: 6013
URI: http://sure.sunderland.ac.uk/id/eprint/6013

Users with ORCIDS

ORCID for Shafiq Ahmed: ORCID iD orcid.org/0000-0001-8701-6889

Catalogue record

Date Deposited: 17 Feb 2016 12:36
Last Modified: 18 Dec 2019 15:38

Contributors

Author: Shafiq Ahmed ORCID iD
Author: J Ford
Author: S Allison
Author: M Jiang
Author: J Milner

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences

Subjects

Sciences

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