title: RSK2 mediates NF-{kappa}B activity through the phosphorylation of IkappaBalpha in the TNF-R1 pathway.
abstract: The ribosomal S6 kinase 2 (RSK2) is a well-known serine/threonine kinase and a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins. It is activated downstream of the MEK/ERKs cascade by mitogenic stimuli such as EGF or TPA. Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser-32, leading to IkappaBalpha degradation. The phosphorylation of IkappaBalpha promotes the activation and translocation of the nuclear factor-kappaB (NF-kappaB) subunits p65 and p50 to the nucleus. The net result is an increased NF-kappaB activity, which serves as a mechanism for RSK2 blockade of TNF-alpha-induced apoptosis and enhanced cell survival.
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Ave N.E., Austin, MN 55912, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Xu
authors.forename: Weihong
authors.initials: W
authors.lastname: Wen
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D053148:Caspase 3; D053181:Caspase 8
references.citation: Nat Rev Cancer. 2002 Jun;2(6):420-30
references.pmid: 12189384
references.citation: Science. 1995 Mar 10;267(5203):1485-8
references.pmid: 7878466
references.citation: Science. 2002 May 31;296(5573):1634-5
references.pmid: 12040173
references.citation: Oncogene. 2007 Nov 15;26(52):7324-32
references.pmid: 17533369
references.citation: Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2438-46
references.pmid: 15223828
references.citation: Curr Biol. 2005 Oct 11;15(19):1762-7
references.pmid: 16213824
references.citation: J Biol Chem. 1999 Sep 17;274(38):27168-76
references.pmid: 10480933
references.citation: Cancer Res. 2002 Mar 1;62(5):1343-8
references.pmid: 11888903
references.citation: Biochem Biophys Res Commun. 1997 Jun 18;235(2):398-402
references.pmid: 9199205
references.citation: Gastroenterology. 2007 Jun;132(7):2489-503
references.pmid: 17570221
references.citation: J Biol Chem. 1999 Feb 5;274(6):3385-95
references.pmid: 9920881
references.citation: Cancer Cell. 2007 Sep;12(3):201-14
references.pmid: 17785202
references.citation: EMBO J. 2000 Jun 15;19(12):2924-34
references.pmid: 10856237
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2489-93
references.pmid: 1532257
references.citation: Oncogene. 2007 Feb 1;26(5):683-700
references.pmid: 16878154
references.citation: Trends Biochem Sci. 1998 Feb;23(2):74-9
references.pmid: 9538693
references.citation: Cell Signal. 2001 Sep;13(9):653-64
references.pmid: 11495723
references.citation: Science. 1996 Aug 16;273(5277):959-63
references.pmid: 8688081
references.citation: Oncogene. 2000 Aug 31;19(37):4221-9
references.pmid: 10980595
references.citation: Nature. 2002 Mar 21;416(6878):345-7
references.pmid: 11907583
references.citation: Cell. 2004 Apr 30;117(3):387-98
references.pmid: 15109498
references.citation: EMBO J. 2002 Oct 15;21(20):5396-407
references.pmid: 12374740
references.citation: J Biol Chem. 1998 Jan 16;273(3):1496-505
references.pmid: 9430688
references.citation: EMBO J. 1998 Sep 1;17(17):5037-47
references.pmid: 9724639
references.citation: EMBO J. 2006 Nov 29;25(23):5549-59
references.pmid: 17110930
references.citation: Cell. 2003 Jul 25;114(2):181-90
references.pmid: 12887920
references.citation: J Biol Chem. 1995 Aug 11;270(32):18848-52
references.pmid: 7642538
references.citation: Cancer Res. 2005 May 1;65(9):3596-603
references.pmid: 15867353
references.citation: Mol Cell Biol. 1996 Mar;16(3):1212-9
references.pmid: 8622665
references.citation: Science. 1999 Nov 12;286(5443):1358-62
references.pmid: 10558990
references.citation: Cancer Res. 2001 May 15;61(10):3908-12
references.pmid: 11358804
references.citation: J Biol Chem. 2007 Mar 16;282(11):8380-92
references.pmid: 17213202
references.citation: Cell. 2002 Apr;109 Suppl:S81-96
references.pmid: 11983155
references.citation: Science. 1999 Aug 6;285(5429):886-91
references.pmid: 10436156
references.citation: Mol Cell. 2008 Sep 5;31(5):722-36
references.pmid: 18775331
references.citation: Genes Dev. 1995 Jul 1;9(13):1586-97
references.pmid: 7628694
references.citation: Science. 1998 Aug 28;281(5381):1305-8
references.pmid: 9721089
references.citation: Annu Rev Immunol. 2000;18:621-63
references.pmid: 10837071
references.citation: Cell. 2001 Feb 23;104(4):487-501
references.pmid: 11239407
references.citation: Mol Cell Biol. 2009 Apr;29(8):2168-80
references.pmid: 19204086
references.citation: Mol Cell Biol. 2001 Aug;21(16):5299-305
references.pmid: 11463813
references.citation: EMBO J. 1999 Dec 1;18(23):6682-93
references.pmid: 10581242
references.citation: Cancer Res. 2007 Sep 1;67(17):8104-12
references.pmid: 17804722
references.citation: Exp Mol Med. 2003 Feb 28;35(1):8-16
references.pmid: 12642898
references.citation: J Biol Chem. 1999 Jan 29;274(5):2893-8
references.pmid: 9915826
references.citation: Oncogene. 2007 May 28;26(25):3745-57
references.pmid: 17530027
references.citation: Novartis Found Symp. 2004;259:102-11; discussion 111-4, 163-9
references.pmid: 15171249