title: S-nitrosylation of ERK inhibits ERK phosphorylation and induces apoptosis.
abstract: Extracellular signal-regulated kinase (ERK) belongs to the mitogen-activated protein kinases (MAPK) superfamily. Aberrant upregulation and activation of ERK cascades may often lead to tumor cell development. However, how ERK is involved in tumor progression is yet to be defined. In current study, we described that ERK undergoes S-nitrosylation by nitric oxide (NO). ERK S-nitrosylation inhibits its phosphorylation and triggers apoptotic program as verified by massive apoptosis in fluorescence staining. The proapoptotic effect of NO induced S-nitrosylation is reversed by NO scavenger Haemoglobin (HB). Furthermore, an S-nitrosylation dead ERK mutant C183A also demolishes the proapoptotic potential of NO and favors cell survival. Therefore, Cys(183) might be a potential S-nitrosylation site in ERK. In addition, S-nitrosylation is a general phenomenon that regulates ERK activity. These findings identify a novel link between NO-mediated S-nitrosylation and ERK regulation, which provide critical insights into the control of apoptosis and tumor development.
authors: State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, China.
authors: Xiujing
authors: X
authors: Feng
authors: Tingzhe
authors: T
authors: Sun
authors: Yuncheng
authors: Y
authors: Bei
authors: Sen
authors: S
authors: Ding
authors: Wei
authors: W
authors: Zheng
authors: Yan
authors: Y
authors: Lu
authors: Pingping
authors: P
authors: Shen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms; D003545:Cysteine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009569:Nitric Oxide / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases; D003545:Cysteine
references: Cancer Res. 2005 Nov 15;65(22):10338-46
references: 16288023
references: Biol Chem. 2003 Oct-Nov;384(10-11):1365-77
references: 14669980
references: Mol Cell Endocrinol. 2008 Jan 30;282(1-2):39-44
references: 18177996
references: Oncogene. 2001 Aug 16;20(36):5043-53
references: 11526489
references: Br J Cancer. 2000 Mar;82(6):1138-44
references: 10735496
references: Semin Cancer Biol. 2005 Aug;15(4):277-89
references: 15914026
references: J Exp Med. 1995 Apr 1;181(4):1333-43
references: 7535333
references: J Mol Cell Cardiol. 2005 Jan;38(1):163-74
references: 15623433
references: Hepatology. 2000 Oct;32(4 Pt 1):770-8
references: 11003621
references: Hum Gene Ther. 1998 Apr 10;9(6):845-54
references: 9581907
references: Nat Rev Cancer. 2004 Dec;4(12):937-47
references: 15573115
references: Cancer Res. 2006 Jul 1;66(13):6459-62
references: 16818612
references: J Biol Chem. 2003 May 16;278(20):18265-70
references: 12646553
references: Curr Opin Cell Biol. 1996 Apr;8(2):205-15
references: 8791420
references: J Biol Chem. 1996 Mar 15;271(11):6328-32
references: 8626428
references: Nat Struct Mol Biol. 2009 Oct;16(10):1004-5
references: 19809488
references: Antioxid Redox Signal. 2007 Jan;9(1):25-47
references: 17115886
references: Mol Cell Endocrinol. 2010 Jan 27;314(2):213-20
references: 19406201
references: Science. 2002 Aug 16;297(5584):1186-90
references: 12183632
references: World J Hepatol. 2010 Sep 27;2(9):337-44
references: 21161018
references: Oncogene. 2007 May 14;26(22):3291-310
references: 17496923
references: Protein Cell. 2010 Feb;1(2):133-42
references: 21203983
references: Trends Biochem Sci. 1994 Nov;19(11):470-3
references: 7855889
references: Surgery. 1997 Aug;122(2):255-63
references: 9288130
references: Nat Cell Biol. 2008 Jul;10(7):866-73
references: 18552833
references: Mol Carcinog. 1998 Sep;23(1):1-12
references: 9766432
references: Mol Cell Biol. 2006 Aug;26(15):5588-94
references: 16847314
references: Biochem J. 2003 May 1;371(Pt 3):1055-64
references: 12605597
references: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references: 18097445
references: Cancer Biother Radiopharm. 1997 Jun;12(3):167-75
references: 10851463
references: Oncogene. 2006 Feb 16;25(7):972-80
references: 16331277
references: J Biol Chem. 2004 May 7;279(19):20339-44
references: 14990579
references: Free Radic Biol Med. 2010 Mar 15;48(6):749-62
references: 20045723