title: SUMO-1 modification on K166 of polyQ-expanded ataxin-3 strengthens its stability and increases its cytotoxicity.
abstract: Post-translational modification by SUMO was proposed to modulate the pathogenesis of several neurodegenerative diseases. Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by polyQ-expanded ataxin-3. We have previously shown that ataxin-3 was a new target of SUMOylation in vitro and in vivo. Here we identified that the major SUMO-1 binding site was located on lysine 166. SUMOylation did not influence the subcellular localization, ubiquitination or aggregates formation of mutant-type ataxin-3, but partially increased its stability and the cell apoptosis. Our findings revealed the role of ataxin-3 SUMOylation in SCA3/MJD pathogenesis.
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors: Ya-Fang
authors: YF
authors: Zhou
authors: Shu-Sheng
authors: SS
authors: Liao
authors: Ying-Ying
authors: YY
authors: Luo
authors: Jian-Guang
authors: JG
authors: Tang
authors: Jun-Ling
authors: JL
authors: Wang
authors: Li-Fang
authors: LF
authors: Lei
authors: Jing-Wei
authors: JW
authors: Chi
authors: Juan
authors: J
authors: Du
authors: Hong
authors: H
authors: Jiang
authors: Kun
authors: K
authors: Xia
authors: Bei-Sha
authors: BS
authors: Tang
authors: Lu
authors: L
authors: Shen
mesh_terms: D017209:Apoptosis; D000067699:Ataxin-3; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D017827:Machado-Joseph Disease / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation / Q000235:genetics*; D054875:Ubiquitination
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3; D008239:Lysine
references: Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56
references: 18000527
references: J Biol Chem. 2000 Mar 3;275(9):6252-8
references: 10692421
references: Mol Cell. 2005 Apr 1;18(1):1-12
references: 15808504
references: J Mol Biol. 1998 Jul 10;280(2):275-86
references: 9654451
references: EMBO Rep. 2007 Jun;8(6):550-5
references: 17545995
references: Hum Mol Genet. 2010 Jan 1;19(1):181-95
references: 19843541
references: J Biol Chem. 2003 Aug 15;278(33):31043-8
references: 12813045
references: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R173-86
references: 14504263
references: J Cell Biol. 1996 Dec;135(6 Pt 1):1457-70
references: 8978815
references: Mol Cell. 1998 Aug;2(2):233-9
references: 9734360
references: J Biol Chem. 2005 Jun 10;280(23):21942-8
references: 15824120
references: Hum Mol Genet. 2002 May 1;11(9):1075-94
references: 11978767
references: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4330-5
references: 15767577
references: Cell. 2000 Jun 23;101(7):753-62
references: 10892746
references: J Biol Chem. 2010 Feb 26;285(9):6532-7
references: 20064935
references: Hum Mol Genet. 2000 Apr 12;9(6):909-16
references: 10767314
references: Cell. 1997 Jan 10;88(1):97-107
references: 9019411
references: J Biol Chem. 2004 Jun 25;279(26):27233-8
references: 15123604
references: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005 Jun;22(3):242-7
references: 15952105
references: Annu Rev Neurosci. 2007;30:575-621
references: 17417937
references: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14145-50
references: 11121022
references: Arch Neurol. 2000 Apr;57(4):540-4
references: 10768629
references: Science. 2004 Apr 2;304(5667):100-4
references: 15064418
references: Am J Hum Genet. 1995 Oct;57(4):809-16
references: 7573040
references: Mol Biol Cell. 2005 Nov;16(11):5115-26
references: 16120648
references: Nature. 2004 Oct 14;431(7010):805-10
references: 15483602
references: Hum Mol Genet. 2009 Apr 15;18(R1):R40-7
references: 19297400
references: Science. 2009 Jun 5;324(5932):1327-30
references: 19498170
references: Cell. 2001 Sep 21;106(6):735-44
references: 11572779
references: Cell. 2003 Nov 26;115(5):565-76
references: 14651848
references: J Biol Chem. 2009 Aug 7;284(32):21296-306
references: 19497852
references: J Biol Chem. 2006 Apr 14;281(15):9919-24
references: 16464864
references: Oncogene. 2004 Mar 15;23(11):1998-2008
references: 15021887
references: Curr Biol. 2002 Feb 19;12(4):R141-3
references: 11864588
references: Cell Death Differ. 2006 Jan;13(1):96-108
references: 15976810
references: Science. 1997 Sep 26;277(5334):1990-3
references: 9302293
references: Nat Genet. 1994 Nov;8(3):221-8
references: 7874163
references: J Cell Biol. 2002 Feb 18;156(4):595-602
references: 11854305
references: Nat Rev Mol Cell Biol. 2001 Mar;2(3):202-10
references: 11265250
references: Biochim Biophys Acta. 2007 Jun;1773(6):694-706
references: 17475350
references: Community Genet. 2007;10(1):19-26
references: 17167246