Codependent 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.
Eisinger-Mathason
T S Karin
TS
Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Andrade
Josefa
J
Groehler
Angela L
AL
Clark
David E
DE
Muratore-Schroeder
Tara L
TL
Pasic
Lejla
L
Smith
Jeffrey A
JA
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Macara
Ian G
IG
Lannigan
Deborah A
DA
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
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
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15078-83
9844018
J Cell Biol. 1999 Dec 27;147(7):1431-42
10613902
J Cell Biol. 2003 Mar 17;160(6):823-31
12642610
J Biol Chem. 2003 May 16;278(20):18376-83
12618428
Cell Signal. 2001 Sep;13(9):653-64
11495723
Mol Cell Biol. 2002 Apr;22(8):2871-81
11909979
Mol Biol Cell. 2004 Dec;15(12):5383-98
15371533
Curr Biol. 1999 Jul 29-Aug 12;9(15):810-20
10469565
Mol Cell Biol. 2005 Nov;25(21):9520-31
16227602
EMBO J. 2001 Jul 2;20(13):3484-94
11432835
J Biol Chem. 2005 Apr 29;280(17):16925-33
15684421
Oncogene. 2007 Feb 1;26(5):683-700
16878154
Mol Cell Neurosci. 2002 Nov;21(3):463-76
12498787
Mol Pharmacol. 2005 Mar;67(3):757-65
15608143
J Cell Sci. 2006 Aug 1;119(Pt 15):3021-3
16868029
J Biol Chem. 1998 May 22;273(21):13317-23
9582378
Cell. 2004 Apr 30;117(3):387-98
15109498
Neuroscience. 2007 May 11;146(2):562-72
17346899
Mol Cell Biol. 1995 Aug;15(8):4353-63
7623830
Mol Cell Biol. 2003 Jul;23(14):4796-804
12832467
J Biol Chem. 1998 Jan 16;273(3):1496-505
9430688
Cancer Res. 2005 Feb 1;65(3):1027-34
15705904
J Cell Biol. 2007 Apr 23;177(2):253-64
17452529
Mol Biol Cell. 2006 May;17(5):2223-35
16481405
Cell Host Microbe. 2007 Nov 15;2(5):295-305
18005751
Mol Biol Cell. 2002 Jan;13(1):195-210
11809833
Nature. 1988 Aug 25;334(6184):715-8
2842685
Mol Cell Biol. 2001 Nov;21(21):7470-80
11585927
J Biol Chem. 2003 Aug 22;278(34):32367-72
12796492
J Cell Sci. 2005 Dec 1;118(Pt 23):5453-63
16278295
Mol Cell Biol. 1992 Mar;12(3):915-27
1545823
Biochem J. 2007 Jan 1;401(1):29-38
17040210
Genomics. 1999 Dec 15;62(3):332-43
10644430
J Biol Chem. 2002 Aug 2;277(31):27733-41
12016217
Neurology. 2005 Aug 9;65(3):420-5
16087907
Cancer Cell. 2004 May;5(5):429-41
15144951
J Cell Biol. 2005 Jun 20;169(6):871-84
15967811
Breast Cancer Res Treat. 2006 Jan;95(2):185-94
16319987
Mol Microbiol. 2007 Aug;65(3):655-70
17635187
J Cell Biol. 2006 Mar 13;172(6):803-8
16520386
EMBO J. 2003 Jun 2;22(11):2788-97
12773393
Proc Natl Acad Sci U S A. 2007 May 22;104(21):9041-6
17502609
Mol Cell Biol. 2001 Jan;21(1):81-7
11113183
Nat Cell Biol. 2002 Aug;4(8):556-64
12134156
Behav Genet. 2007 Jan;37(1):31-50
17033934
J Biol Chem. 1999 Jan 29;274(5):2893-8
9915826
Mol Biol Cell. 2005 Aug;16(8):3753-63
15930128
J Virol. 2006 Feb;80(4):2019-33
16439558
Microbiol Mol Biol Rev. 2004 Jun;68(2):320-44
15187187
Mol Cell Biol. 2006 Jun;26(12):4586-600
16738324
J Cell Biol. 2000 Dec 11;151(6):1257-68
11121440