biostudies-literatureEisinger-Mathason TSNCI NIH HHSNIGMS NIH HHS722-36https://www.ebi.ac.uk/biostudies/studies/S-EPMC2654589biostudies-literatureUnknown31(5)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.Molecular cellCodependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival.PMC2654589R01 GM037537GM084386R01 GM050526R01 GM084386T32 CA009109T32CA009109-30GM50526R01 GM084386-01Muratore-Schroeder TLLannigan DAGroehler ALShabanowitz JHunt DFMacara IGPasic LEisinger-Mathason TSSmith JAClark DEAndrade JfalseCodependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival.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.2008-01-01T00:00:00Z2008 Sep2020-10-29T10:18:55Z2019-03-27T00:21:10ZS-EPMC26545891877533110.1016/j.molcel.2008.06.025