Arsenite-activated JNK signaling enhances CPEB4-Vinexin interaction to facilitate stress granule assembly and cell survival

PLoS One. 2014 Sep 19;9(9):e107961. doi: 10.1371/journal.pone.0107961. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Arsenites / pharmacology*
  • COS Cells
  • Cell Survival*
  • Chlorocebus aethiops
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins / metabolism
  • Stress, Physiological

Substances

  • Adaptor Proteins, Signal Transducing
  • Arsenites
  • CPEB4 protein, human
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • SORBS3 protein, human
  • JNK Mitogen-Activated Protein Kinases
  • arsenite

Grant support

This work was supported by grants from the National Science Council [NSC 102-2628 B-001-007-MY3, NSC102-2321-B-001-058] and Academia Sinica [AS-103-TP-B05] in Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.