title: Arsenite-activated JNK signaling enhances CPEB4-Vinexin interaction to facilitate stress granule assembly and cell survival.
abstract: Stress granules (SGs) are compartmentalized messenger ribonucleoprotein particles (mRNPs) where translationally repressed mRNAs are stored when cells encounter environmental stress. Cytoplasmic polyadenylation element-binding protein (CPEB)4 is a sequence-specific RNA-binding protein and translational regulator. In keeping with the results obtained from the study of other RNA-binding proteins, we found CPEB4 localized in SGs in various arsenite-treated cells. In this study, we identified that Vinexin, a CPEB4-interacting protein, is a novel component of SGs. Vinexin is a SH3-domain-containing adaptor protein and affects cell migration through its association with Vinculin to localize at focal adhesions (FAs). Unexpectedly, Vinexin is translocated from FAs to SGs under arsenite-induced stress. The recruitment of Vinexin to SGs depends on its interaction with CPEB4 and influences SG formation and cell survival. Arsenite-activated c-Jun N-terminal kinase (JNK) signaling enhances the association between CPEB4 and Vinexin, which consequently facilitates SG localization of Vinexin. Taken together, this study uncovers a novel interaction between a translational regulator and an adaptor protein to influence SG assembly and cell survival.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D019556:COS Cells; D002470:Cell Survival; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009124:Muscle Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018053:Arsenites; C554939:CPEB4 protein, human; D009124:Muscle Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C486523:SORBS3 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; C015001:arsenite