A Novel Role for hSMG-1 in Stress Granule Formation

Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia.
Molecular and Cellular Biology (Impact Factor: 4.78). 09/2011; 31(22):4417-29. DOI: 10.1128/MCB.05987-11
Source: PubMed


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

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    • "SMG1 has been shown recently to be required for the formation of stress granules in the cytoplasm of cells under oxidative stress conditions [26]. The UPF1 protein also colocalizes to these stress granules, but in a form that has not undergone the SMG1-catalyzed activating phosphorylations required for mRNA surveillance activity. "
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