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A novel role for hSMG-1 in stress granule formation

By L. James Brown, Tara L. Roberts, Renee Richards, Rick Woods, Geoff Birrell, Y. C. Lim, Shigeo Ohno, Akio Yamashita, Robert T. Abraham, Nuri Gueven and Martin F. Lavin

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-1’s 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

Topics: Messenger RNA Decay, Protein Kinase, SMG-1 Kinase, Surveillance Complex
Publisher: American Society for Microbiology
Year: 2011
OAI identifier: oai:espace.library.uq.edu.au:UQ:262305

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