title: TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis.
abstract: Cytoplasmic stress granules (SGs) are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of misfolded proteins, and that are formed in response to certain types of stress including ER stress. SG formation contributes to cell survival not only by suppressing translation but also by sequestering some apoptosis regulatory factors. Because cells can be exposed to various stresses simultaneously in vivo, the regulation of SG assembly under multiple stress conditions is important but unknown. Here we report that reactive oxygen species (ROS) such as H2O2 oxidize the SG-nucleating protein TIA1, thereby inhibiting SG assembly. Thus, when cells are confronted with a SG-inducing stress such as ER stress caused by protein misfolding, together with ROS-induced oxidative stress, they cannot form SGs, resulting in the promotion of apoptosis. We demonstrate that the suppression of SG formation by oxidative stress may underlie the neuronal cell death seen in neurodegenerative diseases.
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Arimoto-Matsuzaki
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Saito
authors.affiliation: Division of Cell Signaling and Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Takekawa
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide; D010084:Oxidation-Reduction; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C499367:Tia1 protein, mouse; D006861:Hydrogen Peroxide