Abstract
Stress granules (SGs) are formed in the cytoplasm in response to various toxic agents, and are believed to play a critical role in the regulation of mRNA metabolism during stress. In SGs, mRNAs are stored in an abortive translation initiation complex that can be routed to either translation initiation or degradation. Here, we show that G3BP, a phosphorylation-dependent endoribonuclease that interacts with RasGAP, is recruited to SGs in cells exposed to arsenite. G3BP may thus determine the fate of mRNAs during cellular stress. Remarkably, SG assembly can be either dominantly induced by G3BP overexpression, or on the contrary, inhibited by expressing a central domain of G3BP. This region binds RasGAP and contains serine 149, whose dephosphorylation is induced by arsenite treatment. Critically, a phosphomimetic mutant (S149E) fails to oligomerize and to assemble SGs, whereas a nonphosphorylatable G3BP mutant (S149A) does both. These results suggest that G3BP is an effector of SG assembly, and that Ras signaling contributes to this process by regulating G3BP dephosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Amino Acid Sequence / physiology
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Animals
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Arsenates / pharmacology
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COS Cells
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Hypoxia / drug effects
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Cell Hypoxia / physiology
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Cytoplasmic Granules / enzymology*
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Cytoplasmic Granules / genetics
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DNA Helicases
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Endoribonucleases / genetics
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Endoribonucleases / metabolism*
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Eukaryotic Cells / enzymology*
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology
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HeLa Cells
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Humans
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Mutation / physiology
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Phosphorylation / drug effects
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Poly-ADP-Ribose Binding Proteins
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Protein Structure, Tertiary / drug effects
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Protein Structure, Tertiary / physiology
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RNA Helicases
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RNA Recognition Motif Proteins
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RNA, Messenger / metabolism*
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Serine / metabolism
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Stress, Physiological / enzymology*
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Stress, Physiological / genetics
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ras GTPase-Activating Proteins / genetics
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ras GTPase-Activating Proteins / metabolism*
Substances
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Arsenates
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Carrier Proteins
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Poly-ADP-Ribose Binding Proteins
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RNA Recognition Motif Proteins
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RNA, Messenger
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ras GTPase-Activating Proteins
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Serine
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Endoribonucleases
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DNA Helicases
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G3BP1 protein, human
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RNA Helicases
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arsenic acid