title: SENP1 and SENP2 affect spatial and temporal control of sumoylation in mitosis.
abstract: Sumoylation of centromere, kinetochore, and other mitotic chromosome-associated proteins is essential for chromosome segregation. The mechanisms regulating spatial and temporal sumoylation of proteins in mitosis, however, are not well understood. Here we show that the small ubiquitin-related modifier (SUMO)-specific isopeptidases SENP1 and SENP2 are targeted to kinetochores in mitosis. SENP2 targeting occurs through a mechanism dependent on the Nup107-160 subcomplex of the nuclear pore complex and is modulated through interactions with karyopherin α. Overexpression of SENP2, but not other SUMO-specific isopeptidases, causes a defect in chromosome congression that depends on its precise kinetochore targeting. By altering SENP1 kinetochore associations, however, this effect on chromosome congression could be phenocopied. In contrast, RNA interference-mediated knockdown of SENP1 delays sister chromatid separation at metaphase, whereas SENP2 knockdown produces no detectable phenotypes. Our findings indicate that chromosome segregation depends on precise spatial and temporal control of sumoylation in mitosis and that SENP1 and SENP2 are important mediators of this control.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Caelin
authors.initials: C
authors.lastname: Cubeñas-Potts
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Goeres
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Matunis
mesh_terms: D002503:Centromere / Q000378:metabolism / Q000648:ultrastructure; D020090:Chromosome Segregation; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis; D057054:Molecular Imaging; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D055503:Protein Multimerization; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058207:Sumoylation; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism
chemical_list: C512772:NUP107 protein, human; C440251:NUP160 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D028901:alpha Karyopherins; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human
references.citation: Science. 1996 Jul 12;273(5272):239-42
references.pmid: 8662507
references.citation: J Cell Biol. 2007 Apr 9;177(1):39-49
references.pmid: 17403926
references.citation: Mol Biol Cell. 2011 Dec;22(24):4868-82
references.pmid: 22031293
references.citation: Mol Biol Cell. 1995 Jul;6(7):793-807
references.pmid: 7579695
references.citation: J Biol Chem. 2002 May 31;277(22):19961-6
references.pmid: 11896061
references.citation: Cell Mol Life Sci. 2010 Jul;67(13):2215-30
references.pmid: 20372967
references.citation: Mol Biol Cell. 2004 Jul;15(7):3333-44
references.pmid: 15146057
references.citation: EMBO J. 2007 Apr 4;26(7):1853-64
references.pmid: 17363900
references.citation: Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56
references.pmid: 18000527
references.citation: Nat Rev Mol Cell Biol. 2010 Dec;11(12):861-71
references.pmid: 21102611
references.citation: Mol Cell Biol. 2006 Jun;26(12):4489-98
references.pmid: 16738315
references.citation: Curr Protein Pept Sci. 2012 Aug;13(5):467-81
references.pmid: 22812528
references.citation: Annu Rev Biochem. 2004;73:355-82
references.pmid: 15189146
references.citation: Mol Cell. 2008 Mar 28;29(6):729-41
references.pmid: 18374647
references.citation: Biochem J. 2010 Sep 1;430(2):335-44
references.pmid: 20590526
references.citation: Cell Cycle. 2009 Oct 15;8(20):3406-19
references.pmid: 19823017
references.citation: Genetics. 2001 May;158(1):95-107
references.pmid: 11333221
references.citation: Biochem Biophys Res Commun. 2012 Sep 28;426(3):310-6
references.pmid: 22943854
references.citation: J Cell Biol. 2003 Nov 24;163(4):729-41
references.pmid: 14623866
references.citation: Mol Biol Cell. 2009 Dec;20(24):5260-75
references.pmid: 19864462
references.citation: Nucleus. 2012 Jul 1;3(4):349-58
references.pmid: 22688647
references.citation: J Cell Biol. 2008 Nov 17;183(4):589-95
references.pmid: 19015314
references.citation: Mol Biol Cell. 2009 Jan;20(1):410-8
references.pmid: 18946085
references.citation: Mol Microbiol. 2004 Mar;51(5):1375-87
references.pmid: 14982631
references.citation: Mol Biol Cell. 2006 Sep;17(9):3806-18
references.pmid: 16807356
references.citation: J Biol Chem. 2004 Jan 2;279(1):692-703
references.pmid: 14563852
references.citation: EMBO J. 2005 Jun 15;24(12):2172-82
references.pmid: 15933717
references.citation: J Cell Sci. 2010 Aug 15;123(Pt 16):2823-33
references.pmid: 20663916
references.citation: Genetics. 2001 Oct;159(2):453-70
references.pmid: 11606525
references.citation: Trends Biochem Sci. 2011 Mar;36(3):141-50
references.pmid: 20888775
references.citation: J Biol Chem. 2003 Nov 7;278(45):44113-20
references.pmid: 12941945
references.citation: Mol Cell. 2002 Jun;9(6):1169-82
references.pmid: 12086615
references.citation: Semin Cell Dev Biol. 2012 Jul;23(5):482-91
references.pmid: 22326960
references.citation: Mol Cell Proteomics. 2006 Dec;5(12):2298-310
references.pmid: 17000644
references.citation: Eur J Biochem. 2000 Nov;267(21):6423-7
references.pmid: 11029585
references.citation: Exp Cell Res. 2006 Apr 15;312(7):1042-9
references.pmid: 16469311
references.citation: J Biol Chem. 2007 Sep 7;282(36):26217-24
references.pmid: 17591783
references.citation: Trends Cell Biol. 2004 Oct;14(10):547-56
references.pmid: 15450977
references.citation: Genes Cells. 2011 Jun;16(6):652-69
references.pmid: 21554500
references.citation: Trends Biochem Sci. 2007 Jun;32(6):286-95
references.pmid: 17499995
references.citation: Cell Div. 2008 Jan 24;3:5
references.pmid: 18218095
references.citation: Biochem Biophys Res Commun. 2008 Sep 19;374(2):382-7
references.pmid: 18639523
references.citation: J Cell Biol. 2010 Mar 8;188(5):681-92
references.pmid: 20212317
references.citation: Mol Cell Biol. 2002 Sep;22(18):6498-508
references.pmid: 12192048
references.citation: J Cell Biol. 2008 Feb 11;180(3):493-506
references.pmid: 18268099
references.citation: Nat Rev Cancer. 2010 Dec;10(12):825-41
references.pmid: 21102634
references.citation: Nucleic Acids Res. 2001 Sep 15;29(18):3796-803
references.pmid: 11557811