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A Novel Role for hSMG-1 in Stress Granule Formation

Citation

Brown, JA and Roberts, TL and Richards, R and Woods, R and Birrell, G and Lim, YC and Ohno, S and Yamashita, A and Abraham, RT and Guven, N and Lavin, M, A Novel Role for hSMG-1 in Stress Granule Formation, Molecular and Cellular Biology, 31, (2) pp. 4417 - 4429. ISSN 0270-7306 (2011) [Refereed Article]


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Copyright Statement

Copyright 2011 American Society for Microbiology

DOI: doi:10.1128/MCB.05987-11

Abstract

hSMG-1 is a member of the phosphoinositide 3 kinase-like kinase (PIKK) family with established roles in nonsense-mediated decay (NMD) of mRNA containing premature termination codons and in genotoxic stress responses to DNA damage. We report here a novel role for hSMG-1 in cytoplasmic stress granule (SG) formation. Exposure of cells to stress causing agents led to the localization of hSMG-1 to SG, identified by colocalization with TIA-1, G3BP1, and eIF4G. hSMG-1 small interfering RNA and the PIKK inhibitor wortmannin prevented formation of a subset of SG, while specific inhibitors of ATM, DNA-PKcs, or mTOR had no effect. Exposure of cells to H2O2 and sodium arsenite induced (S/T)Q phosphorylation of proteins. While Upf2 and Upf1, an essential substrate for hSMG-1 in NMD, were present in SG, NMD-specific Upf1 phosphorylation was not detected in SG, indicating hSMG-1ís role in SG is separate from classical NMD. Thus, SG formation appears more complex than originally envisaged and hSMG-1 plays a central role in this process.

Item Details

Item Type:Refereed Article
Keywords:SMG1 and stress granule formation
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Signal Transduction
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Guven, N (Dr Nuri Guven)
ID Code:79263
Year Published:2011
Web of Science® Times Cited:20
Deposited By:Pharmacy
Deposited On:2012-08-29
Last Modified:2013-03-18
Downloads:0

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