title: SUMO and Parkinson's disease.
abstract: Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein. Small ubiquitin-related modifier (SUMO) immunoreactivity was observed among others in cases with PD. Key disease-associated proteins are SUMO-modified, linking this posttranslational modification to neurodegeneration. SUMOylation and SUMO-mediated mechanisms have been intensively studied in recent years, revealing nuclear and extranuclear functions for SUMO in a variety of cellular processes, including the regulation of transcriptional activity, modulation of signal transduction pathways, and response to cellular stress. This points to a role for SUMO more than just an antagonist to ubiquitin and proteasomal degradation. The identification of risk and age-at-onset gene loci was a breakthrough in PD and promoted the understanding of molecular mechanisms in the pathology. PD has been increasingly linked with mitochondrial dysfunction and impaired mitochondrial quality control. Interestingly, SUMO is involved in many of these processes and up-regulated in response to cellular stress, further emphasizing the importance of SUMOylation in physiology and disease.
authors: Department of Neurology, University Medical Center Goettingen, Waldweg 33, 37073, Goettingen, Germany, keckerm@gwdg.de.
authors: Katrin
authors: K
authors: Eckermann
mesh_terms: D059290:Dopaminergic Neurons / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D015513:Oncogene Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D015398:Signal Transduction / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D015513:Oncogene Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; D051844:alpha-Synuclein; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D046988:Proteasome Endopeptidase Complex
references: Cell. 1998 Oct 2;95(1):29-39
references: 9778245
references: Pathol Int. 2012 Jun;62(6):407-11
references: 22612509
references: Science. 1997 Jun 27;276(5321):2045-7
references: 9197268
references: Nat Cell Biol. 2002 Feb;4(2):160-4
references: 11813001
references: Ann Neurol. 2000 Apr;47(4):521-3
references: 10762166
references: Mol Cell. 2011 Apr 8;42(1):62-74
references: 21474068
references: Neurosci Lett. 2006 Mar 20;396(1):57-61
references: 16356647
references: Acta Neuropathol. 2008 Dec;116(6):603-14
references: 18836734
references: Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56
references: 18000527
references: Biochem Biophys Res Commun. 2004 May 7;317(3):722-8
references: 15081400
references: J Biol Chem. 2001 Nov 2;276(44):40389-95
references: 11384992
references: J Cell Biol. 2010 Feb 22;188(4):505-13
references: 20156966
references: J Neurochem. 2008 Jul;106(1):464-74
references: 18397367
references: Science. 2003 Jan 10;299(5604):256-9
references: 12446870
references: Physiol Behav. 2007 Sep 10;92(1-2):46-53
references: 17599367
references: Biochem J. 2012 Oct 15;447(2):261-9
references: 22871147
references: Nat Genet. 1999 May;22(1):110-4
references: 10319874
references: Biochem Biophys Res Commun. 1997 Feb 13;231(2):509-13
references: 9070310
references: Nat Cell Biol. 2006 Sep;8(9):986-93
references: 16906147
references: Oncogene. 2003 Aug 14;22(34):5348-57
references: 12917636
references: Mol Med. 1995 Jan;1(2):142-52
references: 8529093
references: Int J Clin Exp Pathol. 2011 Mar;4(3):215-29
references: 21487518
references: Nat Commun. 2012;3:1296
references: 23250426
references: Science. 2003 Oct 31;302(5646):841
references: 14593171
references: J Biol Chem. 2005 Apr 15;280(15):14733-40
references: 15671022
references: J Biomol Screen. 2013 Jun;18(5):621-8
references: 23470489
references: Mol Cell Neurosci. 2008 Feb;37(2):335-45
references: 18035555
references: Curr Biol. 2005 Sep 6;15(17):1578-82
references: 16139214
references: FEBS Lett. 2005 Sep 12;579(22):5007-12
references: 16122737
references: Neuroreport. 2002 Dec 3;13(17):2359-64
references: 12488827
references: Cell. 2005 Nov 4;123(3):383-96
references: 16269331
references: EMBO J. 2002 Jun 3;21(11):2682-91
references: 12032081
references: Cell Cycle. 2011 Sep 15;10(18):3176-88
references: 21900752
references: Neuroreport. 2000 Aug 21;11(12):2635-8
references: 10976934
references: Acta Neuropathol. 2004 Jun;107(6):489-96
references: 14991385
references: Ann Neurol. 1998 Dec;44(6):935-41
references: 9851438
references: J Neurochem. 1992 Feb;58(2):786-9
references: 1729421
references: Cell Signal. 2011 Jun;23(6):963-8
references: 20969953
references: Cell. 2002 Jan 11;108(1):109-20
references: 11792325
references: J Biol Chem. 2001 Oct 5;276(40):37556-63
references: 11477070
references: PLoS Biol. 2007 Jul;5(7):e172
references: 17579517
references: J Biol Chem. 2010 Jun 11;285(24):18565-74
references: 20395301
references: Hum Mol Genet. 2007 Jan 1;16(1):50-60
references: 17116640
references: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14807-12
references: 17766438
references: Neuropathology. 2009 Apr;29(2):125-31
references: 18647263
references: Nat Commun. 2012 Jun 19;3:911
references: 22713753
references: Cell. 1997 Jan 10;88(1):97-107
references: 9019411
references: Neurotox Res. 2013 Jan;23(1):1-21
references: 23229893
references: J Neurosci. 2005 Feb 23;25(8):2002-9
references: 15728840
references: EMBO J. 1999 Nov 15;18(22):6455-61
references: 10562557
references: Cell. 2007 Nov 2;131(3):584-95
references: 17981124
references: J Biol Chem. 2000 Jun 16;275(24):18586-93
references: 10764746
references: Biochem J. 2011 Jan 1;433(1):155-61
references: 20950277
references: Mol Cell Biol. 2004 Jul;24(13):6021-8
references: 15199155
references: J Biol Chem. 2004 Jun 4;279(23):24873-80
references: 15140884
references: Eur J Neurosci. 2000 Dec;12(12):4181-94
references: 11122330
references: Cell. 1997 Jun 27;89(7):1067-76
references: 9215629
references: Mol Cell. 2012 Jun 29;46(6):759-70
references: 22578841
references: Nat Genet. 1998 Feb;18(2):106-8
references: 9462735
references: Lancet. 2004 Sep 25-Oct 1;364(9440):1167-9
references: 15451224
references: Ann Neurol. 2004 Mar;55(3):439-42
references: 14991825
references: Exp Neurol. 2003 Nov;184(1):436-46
references: 14637113
references: J Biol Chem. 2002 Jan 4;277(1):486-91
references: 11679592
references: J Neurol Sci. 2011 Aug 15;307(1-2):157-61
references: 21641618
references: Am J Pathol. 2002 May;160(5):1655-67
references: 12000718
references: J Biol Chem. 2011 Apr 1;286(13):11649-58
references: 21292769
references: Neurobiol Dis. 2009 Nov;36(2):393-400
references: 19716892
references: J Biol Chem. 2003 Aug 15;278(33):31372-9
references: 12761214
references: Science. 1998 Sep 18;281(5384):1860-3
references: 9743501
references: FASEB J. 2013 Sep;27(9):3414-23
references: 23699175
references: J Cell Biochem. 2006 Jul 1;98(4):895-911
references: 16475184
references: Mol Cell. 2004 Feb 27;13(4):611-7
references: 14992729
references: J Cell Biochem. 1999 Mar 1;72(3):435-44
references: 10022524
references: Science. 2012 Aug 31;337(6098):1062-5
references: 22936770
references: J Biol Chem. 2012 Feb 10;287(7):4790-9
references: 22194612
references: Hum Mol Genet. 2008 Nov 1;17(21):3357-67
references: 18689799
references: Genes Cells. 2004 Nov;9(11):1017-29
references: 15507114
references: Nature. 1997 Aug 28;388(6645):839-40
references: 9278044
references: Hum Mol Genet. 2009 Oct 15;18(R2):R169-76
references: 19808793
references: J Biol Chem. 2013 Mar 29;288(13):9102-11
references: 23404503
references: Am J Physiol Heart Circ Physiol. 2012 Feb 1;302(3):H515-26
references: 22037188
references: J Biol Chem. 2006 Oct 13;281(41):30669-77
references: 16912044
references: J Biol Chem. 2010 Jul 2;285(27):20428-32
references: 20424159
references: Neurosci Lett. 1985 Dec 18;62(3):389-94
references: 3912685
references: Proc Natl Acad Sci U S A. 1985 Apr;82(7):2173-7
references: 3872460
references: J Biol Chem. 2000 Mar 3;275(9):6252-8
references: 10692421
references: Nature. 2011 Jun 2;474(7349):105-8
references: 21532592
references: Mol Cell. 2006 Nov 3;24(3):341-54
references: 17081986
references: Mol Cell. 2003 Apr;11(4):1043-54
references: 12718889
references: Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
references: 12498954
references: Neurosci Lett. 2005 Jun 10-17;381(1-2):74-9
references: 15882793
references: Brain Res. 2011 Mar 24;1381:78-89
references: 21256122
references: J Biol Chem. 2007 Nov 23;282(47):34167-75
references: 17728242
references: J Biol Chem. 2006 Jul 28;281(30):20940-20948
references: 16731528
references: J Biol Chem. 2007 May 4;282(18):13680-91
references: 17331951
references: Science. 2004 Apr 2;304(5667):100-4
references: 15064418
references: PLoS Biol. 2004 Nov;2(11):e362
references: 15502874
references: J Neurosci. 2007 Feb 21;27(8):1868-78
references: 17314283
references: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13225-30
references: 14578449
references: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9691-6
references: 15983381
references: FEBS Lett. 1997 Dec 22;420(1):25-7
references: 9450543
references: Nature. 2002 Sep 12;419(6903):135-41
references: 12226657
references: Cell Biol Int. 2004;28(8-9):609-14
references: 15350595
references: Hum Pathol. 2008 Jan;39(1):87-95
references: 17949781
references: Cancer Cell. 2005 Mar;7(3):263-73
references: 15766664
references: Mol Cancer Res. 2003 Feb;1(4):247-61
references: 12612053
references: Neuromolecular Med. 2009;11(4):268-80
references: 19855946
references: Neurogenetics. 2011 Nov;12(4):263-71
references: 21993715
references: Science. 2000 Feb 18;287(5456):1265-9
references: 10678833
references: J Biol Chem. 2008 Jul 25;283(30):20848-56
references: 18492669
references: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8
references: 15181200
references: Cancer Res. 2006 Sep 15;66(18):9026-35
references: 16982744
references: Free Radic Res. 2005 Oct;39(10):1091-9
references: 16298734
references: J Neurosci. 2008 Nov 26;28(48):12993-3002
references: 19036992
references: Science. 2000 Nov 3;290(5493):985-9
references: 11062131
references: Mol Cell Biol. 2000 Mar;20(5):1784-96
references: 10669754
references: Acta Neuropathol. 2006 Sep;112(3):237-51
references: 16845533
references: Neuropathol Appl Neurobiol. 2006 Oct;32(5):562-6
references: 16972890
references: Can J Neurol Sci. 2010 Mar;37(2):213-8
references: 20437931
references: PLoS Genet. 2013 Apr;9(4):e1003412
references: 23593018
references: Ann Neurol. 2013 Jul;74(1):109-18
references: 23536356
references: Hum Mol Genet. 2005 Jul 15;14(14):2063-73
references: 15944198
references: Ann Neurol. 2004 Feb;55(2):164-73
references: 14755719
references: J Cell Biol. 2008 Dec 1;183(5):795-803
references: 19029340
references: Cell. 2001 Jun 29;105(7):891-902
references: 11439185
references: Nat Cell Biol. 2010 Feb;12(2):119-31
references: 20098416
references: Hum Mol Genet. 1999 Apr;8(4):567-74
references: 10072423
references: Environ Health Perspect. 1984 Apr;55:37-46
references: 6329674
references: J Biol Chem. 2005 Mar 18;280(11):10164-73
references: 15637079
references: Clin Cancer Res. 2007 Jan 1;13(1):27-37
references: 17200335
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61
references: 12855764
references: J Biol Chem. 2011 Feb 11;286(6):4098-106
references: 21097510
references: Front Neural Circuits. 2013 Mar 27;7:52
references: 23543616
references: Free Radic Biol Med. 2012 Aug 15;53(4):983-92
references: 22687462
references: Science. 2009 Jun 5;324(5932):1327-30
references: 19498170
references: J Cell Biol. 2006 Sep 25;174(7):1071-85
references: 17000882
references: Cell Death Differ. 2005 Jul;12(7):724-33
references: 15861194
references: J Clin Invest. 2009 Mar;119(3):650-60
references: 19229105
references: J Biol Chem. 2006 Jun 9;281(23):16117-27
references: 16524884
references: Oncogene. 2001 Jan 4;20(1):1-9
references: 11244500
references: J Neurochem. 2001 May;77(3):929-34
references: 11331421
references: J Biol Chem. 2010 Dec 3;285(49):38214-23
references: 20889974
references: Cell Cycle. 2009 Jan 1;8(1):76-87
references: 19106612
references: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14966-71
references: 15465911
references: Neurology. 2012 Dec 11;79(24):2298-9
references: 23152588
references: Neurobiol Dis. 2005 Nov;20(2):401-11
references: 15894486
references: Cancer Res. 2013 Sep 15;73(18):5742-53
references: 23884910
references: Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21122-7
references: 23213215
references: EMBO Rep. 2004 Feb;5(2):213-8
references: 14749723
references: Sci Rep. 2012;2:1002
references: 23256036
references: J Biol Chem. 2004 Jul 9;279(28):29551-7
references: 15123625
references: Neurochem Res. 2004 Sep;29(9):1715-24
references: 15453267
references: J Neurochem. 2001 Jul;78(1):42-54
references: 11432972
references: J Biol Chem. 2006 Apr 14;281(15):9919-24
references: 16464864
references: Int J Cell Biol. 2012;2012:463756
references: 22956959
references: EMBO J. 1999 Nov 15;18(22):6462-71
references: 10562558
references: Nat Med. 2001 Oct;7(10):1144-50
references: 11590439
references: J Cell Biol. 2007 Sep 10;178(6):1025-38
references: 17846173
references: Toxicol Lett. 1989 Aug;48(2):121-49
references: 2672418
references: Sci Signal. 2011 Jun 21;4(178):rs4
references: 21693764
references: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12022-7
references: 18687899
references: Neuron. 2003 Feb 20;37(4):583-95
references: 12597857
references: J Biol Chem. 2005 Apr 29;280(17):16619-24
references: 15718234
references: FASEB J. 2009 Nov;23(11):3917-27
references: 19638400
references: Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2184-90
references: 17690318
references: J Neural Transm (Vienna). 2004 Dec;111(12):1575-81
references: 15565491
references: J Biol Chem. 2011 Jun 3;286(22):19816-29
references: 21383010
references: Sci Rep. 2012;2:262
references: 22355774
references: J Cell Biol. 2008 Jul 14;182(1):141-55
references: 18606847
references: Cell Death Differ. 2012 Mar;19(3):488-500
references: 21921940
references: Ann Neurol. 1999 May;45(5):668-72
references: 10319893
references: PLoS Biol. 2010 Jan 26;8(1):e1000298
references: 20126261
references: Acta Neuropathol. 2012 Feb;123(2):173-88
references: 22057787
references: Trends Biochem Sci. 1999 Jun;24(6):229-31
references: 10366851
references: Neurobiol Dis. 2013 Mar;51:35-42
references: 23064436
references: J Cell Sci. 2007 Apr 1;120(Pt 7):1178-88
references: 17341580
references: PLoS One. 2009 May 27;4(5):e5701
references: 19492085
references: Neurogenetics. 2008 Jul;9(3):163-72
references: 18335262
references: Nature. 1997 May 15;387(6630):299-303
references: 9153396
references: EMBO J. 2007 Sep 19;26(18):4089-101
references: 17762865
references: J Neurosci. 2002 Aug 15;22(16):7006-15
references: 12177198
references: Nature. 1998 Apr 9;392(6676):605-8
references: 9560156
references: J Biol Chem. 2011 Aug 5;286(31):27342-9
references: 21685386
references: Mol Cell. 2006 Feb 3;21(3):349-57
references: 16455490
references: Exp Neurol. 2003 Jan;179(1):9-16
references: 12504863
references: J Neurosci. 1996 Apr 15;16(8):2488-94
references: 8786425
references: J Neurosci Res. 2006 Nov 15;84(7):1543-54
references: 16955485
references: J Biol Chem. 2010 Feb 26;285(9):5983-92
references: 19955185
references: Nat Rev Neurol. 2013 Jan;9(1):13-24
references: 23183883
references: J Cell Sci. 2012 Dec 1;125(Pt 23):5819-29
references: 22976298
references: J Neurochem. 2011 Jun;117(5):856-67
references: 21426348
references: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6
references: 8248242
references: Neuron. 2002 Dec 19;36(6):1007-19
references: 12495618
references: Brain Res. 2001 Jul 6;906(1-2):135-42
references: 11430870
references: Mamm Genome. 2000 Jun;11(6):417-21
references: 10818204
references: Science. 2004 May 21;304(5674):1158-60
references: 15087508
references: Science. 1983 Feb 25;219(4587):979-80
references: 6823561
references: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16973-8
references: 16287980
references: Hum Mol Genet. 1999 Jan;8(1):81-5
references: 9887334
references: J Cell Biol. 1999 Oct 18;147(2):221-34
references: 10525530
references: J Biol Chem. 2003 Nov 7;278(45):44405-11
references: 12923179
references: J Cell Biol. 1996 Dec;135(6 Pt 1):1457-70
references: 8978815
references: Cell Death Differ. 2009 Mar;16(3):428-38
references: 19023331
references: Psychiatry Res. 1979 Dec;1(3):249-54
references: 298352
references: Curr Biol. 2004 Feb 17;14(4):340-5
references: 14972687
references: J Biol Chem. 2005 Dec 30;280(52):43150-8
references: 16227205
references: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8
references: 15824318
references: Ann Neurol. 2013 Feb;73(2):155-69
references: 23225525
references: Mol Cell Proteomics. 2013 Sep;12(9):2536-50
references: 23750026
references: Nat Neurosci. 2007 Jan;10(1):77-86
references: 17159989
references: Biochem Biophys Res Commun. 2002 Jul 12;295(2):495-500
references: 12150977
references: Biochemistry. 1996 Oct 29;35(43):13709-15
references: 8901511
references: Protein Sci. 2012 Jul;21(7):911-7
references: 22573613
references: Mol Cell. 2012 May 25;46(4):472-83
references: 22503103
references: Am J Hum Genet. 2001 Sep;69(3):629-34
references: 11462174
references: J Neurosci. 1988 Aug;8(8):2804-15
references: 3411354
references: J Biol Chem. 2007 Apr 13;282(15):11521-9
references: 17301055
references: Oncogene. 2011 Mar 3;30(9):1108-16
references: 20972456
references: FEBS Lett. 1994 May 23;345(1):27-32
references: 8194594
references: Mol Cell. 1998 Aug;2(2):233-9
references: 9734360
references: Brain. 2004 Feb;127(Pt 2):420-30
references: 14662519
references: Cancer Res. 2007 May 15;67(10):4630-7
references: 17510388
references: J Biol Chem. 2012 Jun 29;287(27):22969-87
references: 22547060
references: Nat Cell Biol. 2006 Dec;8(12):1424-31
references: 17086174
references: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):45-50
references: 16371476
references: Ann Neurol. 2004 Jan;55(1):113-8
references: 14705119
references: Circ J. 2011;75(11):2513-21
references: 22001293
references: J Biol Chem. 2002 Dec 13;277(50):48984-92
references: 12351643
references: Cell Death Differ. 2006 Jan;13(1):96-108
references: 15976810
references: Mol Cell. 2008 Jun 6;30(5):610-9
references: 18538659
references: J Biol Chem. 2002 Jun 28;277(26):23658-63
references: 11960997
references: Trends Cell Biol. 2002 Apr;12(4):178-84
references: 11978537
references: Nat Struct Mol Biol. 2013 Apr;20(4):525-31
references: 23503365
references: Nature. 1997 May 15;387(6630):296-9
references: 9153395
references: J Mol Biol. 2007 Apr 27;368(2):388-97
references: 17362989
references: Hum Mol Genet. 2010 Jun 15;19(12):2395-408
references: 20304780
references: J Cell Biochem. 2008 Feb 1;103(2):456-70
references: 17661348
references: Neurology. 2001 Feb 27;56(4):555-7
references: 11222808
references: EMBO Rep. 2012 Apr;13(4):378-85
references: 22354088
references: Brain Res. 2007 Dec 12;1184:10-6
references: 17950257
references: J Neurochem. 2007 Mar;100(6):1626-35
references: 17166173
references: J Cell Sci. 2010 Mar 15;123(Pt 6):917-26
references: 20179104
references: EMBO J. 1999 Nov 1;18(21):6037-49
references: 10545115
references: Hum Mol Genet. 2003 Nov 15;12(22):2957-65
references: 14519684
references: Mov Disord. 2010;25 Suppl 1:S49-54
references: 20187257
references: Neurosci Lett. 2013 Jun 7;544:119-24
references: 23583339
references: Biochem J. 2010 May 13;428(2):133-45
references: 20462400
references: Curr Biol. 2005 Sep 6;15(17):1572-7
references: 16139213
references: J Cell Biol. 2011 Jul 11;194(1):49-60
references: 21746851
references: Hum Genet. 1998 Oct;103(4):424-7
references: 9856485
references: Nat Cell Biol. 2007 Nov;9(11):1243-52
references: 17906618
references: Nat Genet. 2000 Jul;25(3):302-5
references: 10888878
references: BMC Genomics. 2010 Jan 11;11:22
references: 20064247
references: Nat Neurosci. 2000 Dec;3(12):1301-6
references: 11100151
references: J Biol Chem. 2006 Feb 10;281(6):3595-603
references: 16332688
references: J Comp Neurol. 2007 Jan 20;500(3):585-99
references: 17120294