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

Eisinger-Mathason TS, Andrade J, Groehler AL, Clark DE, Muratore-Schroeder TL, Pasic L, Smith JA, Shabanowitz J, Hunt DF, Macara IG, Lannigan DA
Mol Cell. 2008 31 (5): 722-36

PMID: 18775331 · PMCID: PMC2654589 · DOI:10.1016/j.molcel.2008.06.025

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.

MeSH Terms (14)

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

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