title: EDD, a ubiquitin-protein ligase of the N-end rule pathway, associates with spindle assembly checkpoint components and regulates the mitotic response to nocodazole.
abstract: In this work, we identify physical and genetic interactions that implicate E3 identified by differential display (EDD) in promoting spindle assembly checkpoint (SAC) function. During mitosis, the SAC initiates a mitotic checkpoint in response to chromosomes with kinetochores unattached to spindle pole microtubules. Similar to Budding uninhibited by benzimidazoles-related 1 (BUBR1) siRNA, a bona fide SAC component, EDD siRNA abrogated G2/M accumulation in response to the mitotic destabilizing agent nocodazole. Furthermore, EDD siRNA reduced mitotic cell viability and, in nocodazole-treated cells, increased expression of the promitotic progression protein cell division cycle 20 (CDC20). Copurification studies also identified physical interactions with CDC20, BUBR1, and other components of the SAC. Taken together, these observations highlight the potential role of EDD in regulating mitotic progression and the cellular response to perturbed mitosis.
authors.affiliation: From the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, Scotland, United Kingdom.
authors.forename: Flavia
authors.initials: F
authors.lastname: Scialpi
authors.affiliation: From the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, Scotland, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Mellis
authors.affiliation: From the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, Scotland, United Kingdom mark.ditzel@ed.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Ditzel
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D064199:Cdc20 Proteins / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D064199:Cdc20 Proteins; C577488:CDC20 protein, human; C117617:UBR5 protein, human; D044767:Ubiquitin-Protein Ligases; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole
keywords: BUB3; BUBR1; CDC20; E3 ubiquitin ligase; EDD; SAC; cell cycle; checkpoint control; chromosomes; mitosis
references.citation: Oncogene. 2013 Sep 26;32(39):4593-601
references.pmid: 23318447
references.citation: Nat Struct Mol Biol. 2012 Nov;19(11):1116-23
references.pmid: 23007861
references.citation: Nat Cell Biol. 2009 Apr;11(4):409-19
references.pmid: 19287380
references.citation: Nat Struct Mol Biol. 2012 Mar 11;19(4):387-94
references.pmid: 22407014
references.citation: J Biol Chem. 2010 Apr 16;285(16):11800-9
references.pmid: 20167605
references.citation: J Biol Chem. 2006 Dec 29;281(52):39990-40000
references.pmid: 17074762
references.citation: Nature. 1979 Feb 22;277(5698):665-7
references.pmid: 423966
references.citation: Blood. 2013 Apr 18;121(16):3161-4
references.pmid: 23407552
references.citation: J Biol Chem. 2011 Apr 29;286(17):14972-82
references.pmid: 21383020
references.citation: Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12091-6
references.pmid: 25092319
references.citation: Cell. 2010 Sep 3;142(5):810-21
references.pmid: 20813266
references.citation: PLoS Genet. 2008 Feb 29;4(2):e1000015
references.pmid: 18454191
references.citation: Curr Biol. 2010 Sep 28;20(18):1666-71
references.pmid: 20832310
references.citation: J Biol Chem. 2002 Jul 19;277(29):26468-78
references.pmid: 12011095
references.citation: Cell Biol Int Rep. 1977 Mar;1(2):177-83
references.pmid: 343926
references.citation: Cell Cycle. 2012 Feb 15;11(4):715-20
references.pmid: 22374670
references.citation: J Cell Biol. 2007 May 7;177(3):413-24
references.pmid: 17485487
references.citation: Mol Cell. 2012 Sep 28;47(6):921-32
references.pmid: 22940250
references.citation: Cancer Res. 2004 Feb 1;64(3):942-51
references.pmid: 14871824
references.citation: Mol Cell Biol. 2005 May;25(10):4046-61
references.pmid: 15870277
references.citation: Dev Biol. 1994 Oct;165(2):507-26
references.pmid: 7958417
references.citation: Mol Biol Cell. 2011 Feb 1;22(3):399-411
references.pmid: 21118991
references.citation: Nature. 2013 Feb 28;494(7438):502-5
references.pmid: 23389450
references.citation: J Cell Biol. 2003 Apr 28;161(2):267-80
references.pmid: 12719470
references.citation: Methods Mol Biol. 2011;761:151-61
references.pmid: 21755447
references.citation: Blood. 2004 Feb 15;103(4):1278-85
references.pmid: 14576056
references.citation: Mol Cell Biol. 1998 Feb;18(2):1055-64
references.pmid: 9448003
references.citation: Methods Mol Biol. 2006;314:73-80
references.pmid: 16673875
references.citation: Nat Rev Mol Cell Biol. 2013 Apr;14(4):197-210
references.pmid: 23847781
references.citation: Mol Cell Biol. 2004 Aug;24(16):7225-34
references.pmid: 15282321
references.citation: Cell. 2012 Aug 17;150(4):697-709
references.pmid: 22884692
references.citation: Science. 2011 Sep 30;333(6051):1895-8
references.pmid: 21960636
references.citation: Genes Dev. 1998 Aug 15;12(16):2549-59
references.pmid: 9716407
references.citation: J Cell Biol. 1999 Sep 6;146(5):941-54
references.pmid: 10477750
references.citation: Nat Rev Mol Cell Biol. 2011 Oct 21;12(11):735-47
references.pmid: 22016057
references.citation: Cell Cycle. 2007 Dec 15;6(24):3070-7
references.pmid: 18073532
references.citation: Cell. 1990 Dec 21;63(6):1129-36
references.pmid: 2175676
references.citation: Philos Trans R Soc Lond B Biol Sci. 2011 Dec 27;366(1584):3595-604
references.pmid: 22084386
references.citation: Cell. 1998 Feb 6;92(3):401-13
references.pmid: 9476899
references.citation: EMBO J. 2009 Jul 22;28(14):2077-89
references.pmid: 19407811
references.citation: Curr Biol. 2012 Nov 20;22(22):R966-80
references.pmid: 23174302
references.citation: Dev Cell. 2004 Jul;7(1):45-60
references.pmid: 15239953
references.citation: Genes Dev. 2007 Feb 15;21(4):420-35
references.pmid: 17322402
references.citation: Dev Biol. 1977 Feb;55(2):213-32
references.pmid: 402295
references.citation: Development. 2002 Dec;129(24):5697-706
references.pmid: 12421709
references.citation: Radiat Res. 2003 Jun;159(6):759-67
references.pmid: 12751958
references.citation: Nat Rev Cancer. 2009 Jun;9(6):400-14
references.pmid: 19440234