A Novel Role for hSMG-1 in Stress Granule Formation

被引：40

作者：

Brown, James A. L. ^{[1
,2
]}

Roberts, Tara L. ^{[1
,3
]}

Richards, Renee ^{[1
,3
]}

Woods, Rick ^{[1
]}

Birrell, Geoff ^{[1
]}

Lim, Y. C. ^{[1
,3
]}

Ohno, Shigeo ^{[4
]}

Yamashita, Akio ^{[4
]}

Abraham, Robert T. ^{[5
]}

Gueven, Nuri ^{[1
]}

Lavin, Martin F. ^{[1
,3
]}

机构：

[1] Queensland Inst Med Res, Radiat Biol & Oncol Lab, Brisbane, Qld 4029, Australia

[2] Natl Univ Ireland, Chromosome Biol Ctr, Galway, Ireland

[3] Univ Queensland, Clin Res Ctr, Brisbane, Qld 4029, Australia

[4] Yokohama City Univ, Sch Med, Dept Mol Biol, Yokohama, Kanagawa 2360004, Japan

[5] Wyeth Oncol Res, Pearl River, NY 10965 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2011年 / 31卷 / 22期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

MESSENGER-RNA DECAY; PROTEIN-KINASE; SMG-1; KINASE; SURVEILLANCE COMPLEX; SOMATIC MUTATIONS; NMD FACTORS; PHOSPHORYLATION; INHIBITION; SITES; ATM;

D O I：

10.1128/MCB.05987-11

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4417 / 4429

页数：13

共 60 条

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