title: Arginine methylation-dependent regulation of ASK1 signaling by PRMT1.
abstract: Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is implicated in modulation of cellular processes including gene transcription. The role of PRMTs in the regulation of intracellular signaling pathways has remained obscure, however. We now show that PRMT1 methylates apoptosis signal-regulating kinase 1 (ASK1) at arginine residues 78 and 80 and thereby negatively regulates ASK1 signaling. PRMT1-mediated ASK1 methylation attenuated the H(2)O(2)-induced stimulation of ASK1, with this inhibitory effect of PRMT1 being abolished by replacement of arginines 78 and 80 of ASK1 with lysine. Furthermore, depletion of PRMT1 expression by RNA interference potentiated H(2)O(2)-induced stimulation of ASK1. PRMT1-mediated ASK1 methylation promoted the interaction between ASK1 and its negative regulator thioredoxin, whereas it abrogated the association of ASK1 with its positive regulator TRAF2. Moreover, PRMT1 depletion potentiated paclitaxel-induced ASK1 activation and apoptosis in human breast cancer cells. Together, our results indicate that arginine methylation of ASK1 by PRMT1 contributes to the regulation of stress-induced signaling that controls a variety of cellular events including apoptosis.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Cho
authors.forename: M-K
authors.initials: MK
authors.lastname: Lee
authors.forename: K W
authors.initials: KW
authors.lastname: Yoon
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: S-G
authors.initials: SG
authors.lastname: Cho
authors.forename: E-J
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D016297:Mutagenesis, Site-Directed; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human
references.citation: J Biol Chem. 2001 Apr 20;276(16):12749-55
references.pmid: 11278289
references.citation: Mol Cell Biol. 2002 Nov;22(22):7721-30
references.pmid: 12391142
references.citation: J Cell Biol. 2003 Oct 13;163(1):71-81
references.pmid: 14557248
references.citation: Oncogene. 1999 Jan 7;18(1):173-80
references.pmid: 9926932
references.citation: J Biol Chem. 1996 Jun 21;271(25):15034-44
references.pmid: 8663146
references.citation: EMBO J. 1999 Mar 1;18(5):1223-34
references.pmid: 10064589
references.citation: Mol Cell. 2005 Apr 29;18(3):263-72
references.pmid: 15866169
references.citation: EMBO J. 2001 Feb 1;20(3):446-56
references.pmid: 11157751
references.citation: J Biol Chem. 2007 Nov 9;282(45):33009-21
references.pmid: 17848568
references.citation: J Biol Chem. 2004 Oct 15;279(42):43589-94
references.pmid: 15299005
references.citation: Cell Death Differ. 2007 Aug;14(8):1518-28
references.pmid: 17541429
references.citation: J Biol Chem. 2003 Jun 27;278(26):23432-40
references.pmid: 12697749
references.citation: Biochim Biophys Acta. 2008 Nov;1780(11):1325-36
references.pmid: 18206122
references.citation: Int J Cancer. 2011 Feb 1;128(3):562-73
references.pmid: 20473859
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:199-225
references.pmid: 17883330
references.citation: Science. 1997 Jan 3;275(5296):90-4
references.pmid: 8974401
references.citation: Mol Cell Biol. 2001 Feb;21(3):893-901
references.pmid: 11154276
references.citation: J Cell Physiol. 2002 Apr;191(1):95-104
references.pmid: 11920685
references.citation: Mol Cell Biol. 2007 Dec;27(23):8152-63
references.pmid: 17724081
references.citation: Tumour Biol. 2011 Jun;32(3):575-82
references.pmid: 21229402
references.citation: EMBO J. 1998 May 1;17(9):2596-606
references.pmid: 9564042
references.citation: Cell. 2001 Jul 13;106(1):5-8
references.pmid: 11461695
references.citation: J Biol Chem. 2005 Nov 4;280(44):37033-40
references.pmid: 16129676
references.citation: J Biol Chem. 1998 Feb 27;273(9):4928-36
references.pmid: 9478937
references.citation: Science. 1998 Sep 18;281(5384):1860-3
references.pmid: 9743501
references.citation: Mol Cell. 2009 Jan 16;33(1):1-13
references.pmid: 19150423
references.citation: J Biol Chem. 2000 Aug 25;275(34):26576-81
references.pmid: 10849426
references.citation: J Biol Chem. 2000 Mar 17;275(11):7723-30
references.pmid: 10713084
references.citation: Mol Cell Biol. 2000 Mar;20(6):2198-208
references.pmid: 10688666
references.citation: Genes Dev. 2011 Jan 15;25(2):176-88
references.pmid: 21245169
references.citation: Nat Cell Biol. 2007 Oct;9(10):1208-15
references.pmid: 17891136
references.citation: Sci STKE. 2005 Feb 15;2005(271):re2
references.pmid: 15713950
references.citation: EMBO Rep. 2001 Mar;2(3):222-8
references.pmid: 11266364
references.citation: Mol Cell Biol. 2000 Jul;20(13):4859-69
references.pmid: 10848611
references.citation: Mol Cell. 2008 Jul 25;31(2):212-21
references.pmid: 18657504
references.citation: J Clin Invest. 2003 Jun;111(12):1933-43
references.pmid: 12813029
references.citation: Mol Cell. 2008 Oct 24;32(2):221-31
references.pmid: 18951090
references.citation: Anticancer Res. 2009 Apr;29(4):1361-6
references.pmid: 19414388
references.citation: J Biol Chem. 2004 Feb 27;279(9):7584-90
references.pmid: 14668338