Phosphorylation of HuR by Chk2 Regulates SIRT1 Expression

Abdelmohsen, K., Pullmann Jr., R., Lal, A., Kim, H.H., Galban, S., Yang, X., Blethrow, J.D., Walker, M., Shubert, J. and Gillespie, D.A. (2007) Phosphorylation of HuR by Chk2 Regulates SIRT1 Expression. Molecular Cell, 25(4), pp. 543-557. (doi:10.1016/j.molcel.2007.01.011)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1016/j.molcel.2007.01.011

Abstract

The RNA binding protein HuR regulates the stability of many target mRNAs. Here, we report that HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels. Unexpectedly, oxidative stress triggered the dissociation of the [HuR-SIRT1 mRNA] complex, in turn promoting SIRT1 mRNA decay, reducing SIRT1 abundance, and lowering cell survival. The cell cycle checkpoint kinase Chk2 was activated by H2O2, interacted with HuR, and was predicted to phosphorylate HuR at residues S88, S100, and T118. Mutation of these residues revealed a complex pattern of HuR binding, with S100 appearing to be important for [HuR-SIRT1 mRNA] dissociation after H2O2. Our findings demonstrate that HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gillespie, Professor David
Authors: Abdelmohsen, K., Pullmann Jr., R., Lal, A., Kim, H.H., Galban, S., Yang, X., Blethrow, J.D., Walker, M., Shubert, J., and Gillespie, D.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular Cell
ISSN:1097-2765

University Staff: Request a correction | Enlighten Editors: Update this record