title: A novel role for hSMG-1 in stress granule formation.
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.
authors.affiliation: Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia.
authors.forename: James A L
authors.initials: JA
authors.lastname: Brown
authors.forename: Tara L
authors.initials: TL
authors.lastname: Roberts
authors.forename: Renee
authors.initials: R
authors.lastname: Richards
authors.forename: Rick
authors.initials: R
authors.lastname: Woods
authors.forename: Geoff
authors.initials: G
authors.lastname: Birrell
authors.forename: Y C
authors.initials: YC
authors.lastname: Lim
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: Akio
authors.initials: A
authors.lastname: Yamashita
authors.forename: Robert T
authors.initials: RT
authors.lastname: Abraham
authors.forename: Nuri
authors.initials: N
authors.lastname: Gueven
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D004249:DNA Damage; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017670:Sodium Compounds / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*; D000074019:T-Cell Intracellular Antigen-1; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018053:Arsenites; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; D000081082:Phosphoinositide-3 Kinase Inhibitors; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017670:Sodium Compounds; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C468286:UPF2 protein, human; C017947:sodium arsenite; D006861:Hydrogen Peroxide; C546842:MTOR protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human; D000077191:Wortmannin