A novel role for hsmg-1 in stress granule formation
Brown, J. A. L.
Roberts, T. L.
Lim, Y. C.
Abraham, R. T.
Lavin, M. F.
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Brown, J. A. L. Roberts, T. L.; Richards, R.; Woods, R.; Birrell, G.; Lim, Y. C.; Ohno, S.; Yamashita, A.; Abraham, R. T.; Gueven, N.; Lavin, M. F. (2011). A novel role for hsmg-1 in stress granule formation. Molecular and Cellular Biology 31 (22), 4417-4429
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-PK(cs), or mTOR had no effect. Exposure of cells to H(2)O(2) 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.