title: Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival.
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.
authors.affiliation: Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: T S Karin
authors.initials: TS
authors.lastname: Eisinger-Mathason
authors.forename: Josefa
authors.initials: J
authors.lastname: Andrade
authors.forename: Angela L
authors.initials: AL
authors.lastname: Groehler
authors.forename: David E
authors.initials: DE
authors.lastname: Clark
authors.forename: Tara L
authors.initials: TL
authors.lastname: Muratore-Schroeder
authors.forename: Lejla
authors.initials: L
authors.lastname: Pasic
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Smith
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lannigan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005260:Female; D006801:Humans; D018384:Oxidative Stress; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D039102:Poly(A)-Binding Proteins; D011328:Prions; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D019938:Cyclin D1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15078-83
references.pmid: 9844018
references.citation: J Cell Biol. 1999 Dec 27;147(7):1431-42
references.pmid: 10613902
references.citation: J Cell Biol. 2003 Mar 17;160(6):823-31
references.pmid: 12642610
references.citation: J Biol Chem. 2003 May 16;278(20):18376-83
references.pmid: 12618428
references.citation: Cell Signal. 2001 Sep;13(9):653-64
references.pmid: 11495723
references.citation: Mol Cell Biol. 2002 Apr;22(8):2871-81
references.pmid: 11909979
references.citation: Mol Biol Cell. 2004 Dec;15(12):5383-98
references.pmid: 15371533
references.citation: Curr Biol. 1999 Jul 29-Aug 12;9(15):810-20
references.pmid: 10469565
references.citation: Mol Cell Biol. 2005 Nov;25(21):9520-31
references.pmid: 16227602
references.citation: EMBO J. 2001 Jul 2;20(13):3484-94
references.pmid: 11432835
references.citation: J Biol Chem. 2005 Apr 29;280(17):16925-33
references.pmid: 15684421
references.citation: Oncogene. 2007 Feb 1;26(5):683-700
references.pmid: 16878154
references.citation: Mol Cell Neurosci. 2002 Nov;21(3):463-76
references.pmid: 12498787
references.citation: Mol Pharmacol. 2005 Mar;67(3):757-65
references.pmid: 15608143
references.citation: J Cell Sci. 2006 Aug 1;119(Pt 15):3021-3
references.pmid: 16868029
references.citation: J Biol Chem. 1998 May 22;273(21):13317-23
references.pmid: 9582378
references.citation: Cell. 2004 Apr 30;117(3):387-98
references.pmid: 15109498
references.citation: Neuroscience. 2007 May 11;146(2):562-72
references.pmid: 17346899
references.citation: Mol Cell Biol. 1995 Aug;15(8):4353-63
references.pmid: 7623830
references.citation: Mol Cell Biol. 2003 Jul;23(14):4796-804
references.pmid: 12832467
references.citation: J Biol Chem. 1998 Jan 16;273(3):1496-505
references.pmid: 9430688
references.citation: Cancer Res. 2005 Feb 1;65(3):1027-34
references.pmid: 15705904
references.citation: J Cell Biol. 2007 Apr 23;177(2):253-64
references.pmid: 17452529
references.citation: Mol Biol Cell. 2006 May;17(5):2223-35
references.pmid: 16481405
references.citation: Cell Host Microbe. 2007 Nov 15;2(5):295-305
references.pmid: 18005751
references.citation: Mol Biol Cell. 2002 Jan;13(1):195-210
references.pmid: 11809833
references.citation: Nature. 1988 Aug 25;334(6184):715-8
references.pmid: 2842685
references.citation: Mol Cell Biol. 2001 Nov;21(21):7470-80
references.pmid: 11585927
references.citation: J Biol Chem. 2003 Aug 22;278(34):32367-72
references.pmid: 12796492
references.citation: J Cell Sci. 2005 Dec 1;118(Pt 23):5453-63
references.pmid: 16278295
references.citation: Mol Cell Biol. 1992 Mar;12(3):915-27
references.pmid: 1545823
references.citation: Biochem J. 2007 Jan 1;401(1):29-38
references.pmid: 17040210
references.citation: Genomics. 1999 Dec 15;62(3):332-43
references.pmid: 10644430
references.citation: J Biol Chem. 2002 Aug 2;277(31):27733-41
references.pmid: 12016217
references.citation: Neurology. 2005 Aug 9;65(3):420-5
references.pmid: 16087907
references.citation: Cancer Cell. 2004 May;5(5):429-41
references.pmid: 15144951
references.citation: J Cell Biol. 2005 Jun 20;169(6):871-84
references.pmid: 15967811
references.citation: Breast Cancer Res Treat. 2006 Jan;95(2):185-94
references.pmid: 16319987
references.citation: Mol Microbiol. 2007 Aug;65(3):655-70
references.pmid: 17635187
references.citation: J Cell Biol. 2006 Mar 13;172(6):803-8
references.pmid: 16520386
references.citation: EMBO J. 2003 Jun 2;22(11):2788-97
references.pmid: 12773393
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):9041-6
references.pmid: 17502609
references.citation: Mol Cell Biol. 2001 Jan;21(1):81-7
references.pmid: 11113183
references.citation: Nat Cell Biol. 2002 Aug;4(8):556-64
references.pmid: 12134156
references.citation: Behav Genet. 2007 Jan;37(1):31-50
references.pmid: 17033934
references.citation: J Biol Chem. 1999 Jan 29;274(5):2893-8
references.pmid: 9915826
references.citation: Mol Biol Cell. 2005 Aug;16(8):3753-63
references.pmid: 15930128
references.citation: J Virol. 2006 Feb;80(4):2019-33
references.pmid: 16439558
references.citation: Microbiol Mol Biol Rev. 2004 Jun;68(2):320-44
references.pmid: 15187187
references.citation: Mol Cell Biol. 2006 Jun;26(12):4586-600
references.pmid: 16738324
references.citation: J Cell Biol. 2000 Dec 11;151(6):1257-68
references.pmid: 11121440