A novel role for hsmg-1 in stress granule formation
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.
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.
Publication Date
2011-09-12
Type
Article
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Citation
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
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-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.
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Publisher
American Society for Microbiology
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Attribution-NonCommercial-NoDerivs 3.0 Ireland