The RasGAP-associated Endoribonuclease G3BP Assembles Stress Granules

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Mar 19

PMID 12642610

Citations 514

Authors

Helene Tourriere

Karim Chebli

Latifa Zekri

Brice Courselaud

Jean Marie Blanchard

Edouard Bertrand

Jamal Tazi

Affiliations

Soon will be listed here.

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.

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