Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival

Mol Cell. 2008 Sep 5;31(5):722-36. doi: 10.1016/j.molcel.2008.06.025.

Abstract

Stress granules aid cell survival in response to environmental stressors by acting as sites of translational repression. We report an unanticipated link between stress granules and the serine/threonine kinase RSK2. In stressed breast cells, endogenous RSK2 colocalizes in granules with TIA-1 and poly(A)-binding protein 1, and the sequestration of RSK2 and TIA-1 exhibits codependency. The RSK2 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA-1. Silencing RSK2 decreases cell survival in response to stress. Mitogen releases RSK2 from the stress granules and permits its nuclear import via a nucleocytoplasmic shuttling sequence in the C-terminal domain. Nuclear accumulation is dependent on TIA-1. Surprisingly, nuclear localization of RSK2 is sufficient to enhance proliferation through induction of cyclin D1, in the absence of other active signaling pathways. Hence, RSK2 is a pivotal factor linking the stress response to survival and proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Survival*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cytoplasmic Granules / metabolism*
  • Female
  • Humans
  • Oxidative Stress
  • Poly(A)-Binding Proteins / genetics
  • Poly(A)-Binding Proteins / metabolism*
  • Prions / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • T-Cell Intracellular Antigen-1

Substances

  • Poly(A)-Binding Proteins
  • Prions
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • Cyclin D1
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3