TY - JOUR
T1 - A novel role for hSMG-1 in stress granule formation
AU - Brown, James A.L.
AU - Roberts, Tara L.
AU - Richards, Renee
AU - Woods, Rick
AU - Birrell, Geoff
AU - Lim, Y. C.
AU - Ohno, Shigeo
AU - Yamashita, Akio
AU - Abraham, Robert T.
AU - Gueven, Nuri
AU - Lavin, Martin F.
PY - 2011/11
Y1 - 2011/11
N2 - 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 2O 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.
AB - 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 2O 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.
UR - http://www.scopus.com/inward/record.url?scp=83255185785&partnerID=8YFLogxK
U2 - 10.1128/MCB.05987-11
DO - 10.1128/MCB.05987-11
M3 - Article
C2 - 21911475
AN - SCOPUS:83255185785
SN - 0270-7306
VL - 31
SP - 4417
EP - 4429
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 22
ER -