title: Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation.
abstract: Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase-promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2A(B56) allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2A(B56) also stabilizes kinetochore-microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2-E3 interplay to coordinate ubiquitination with critical events during cell division.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Allison
authors.initials: A
authors.lastname: Craney
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Aileen
authors.initials: A
authors.lastname: Kelly
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Luying
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Indro
authors.initials: I
authors.lastname: Fedrigo
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720 mrape@berkeley.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Rape
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D055162:Biocatalysis; D064199:Cdc20 Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D064199:Cdc20 Proteins; D025801:Ubiquitin; D012694:Serine; D064173:Anaphase-Promoting Complex-Cyclosome; D054648:Protein Phosphatase 2
keywords: APC/C; Ube2S; anaphase-promoting complex; phosphorylation; ubiquitin
references.citation: Mol Cell. 2003 Jul;12(1):87-100
references.pmid: 12887895
references.citation: Nat Cell Biol. 2004 Mar;6(3):232-7
references.pmid: 14767480
references.citation: Mol Cell. 2004 Nov 5;16(3):387-97
references.pmid: 15525512
references.citation: Mol Cell. 2005 May 27;18(5):543-53
references.pmid: 15916961
references.citation: Nat Struct Mol Biol. 2005 Oct;12(10):933-4
references.pmid: 16142244
references.citation: Nat Cell Biol. 2006 Jul;8(7):700-10
references.pmid: 16799550
references.citation: Nat Med. 2006 Jul;12(7):809-16
references.pmid: 16819549
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
references.pmid: 16896351
references.citation: Cell. 2008 May 16;133(4):653-65
references.pmid: 18485873
references.citation: Science. 2009 Mar 13;323(5920):1477-81
references.pmid: 19286556
references.citation: Annu Rev Biochem. 2009;78:399-434
references.pmid: 19489725
references.citation: Cell. 2009 Jul 23;138(2):389-403
references.pmid: 19615732
references.citation: Nat Cell Biol. 2009 Nov;11(11):1363-9
references.pmid: 19820702
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18213-8
references.pmid: 19822757
references.citation: Nat Rev Mol Cell Biol. 2009 Nov;10(11):755-64
references.pmid: 19851334
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1355-60
references.pmid: 20080579
references.citation: Science. 2010 Apr 30;328(5978):593-9
references.pmid: 20360068
references.citation: Mol Cell. 2010 Aug 13;39(3):477-84
references.pmid: 20655260
references.citation: Nat Cell Biol. 2010 Sep;12(9):886-93
references.pmid: 20711181
references.citation: Nature. 2011 Feb 10;470(7333):274-8
references.pmid: 21107322
references.citation: Nat Struct Mol Biol. 2011 Jan;18(1):6-13
references.pmid: 21186364
references.citation: Cell. 2011 Mar 4;144(5):769-81
references.pmid: 21376237
references.citation: Semin Cell Dev Biol. 2011 Aug;22(6):551-8
references.pmid: 21439394
references.citation: Mol Cell. 2011 Jun 24;42(6):744-57
references.pmid: 21700221
references.citation: Nat Cell Biol. 2011 Aug 28;13(10):1265-71
references.pmid: 21874008
references.citation: PLoS One. 2011;6(11):e27099
references.pmid: 22087249
references.citation: Nature. 2012 Mar 21;484(7393):208-13
references.pmid: 22437499
references.citation: Dev Cell. 2012 May 15;22(5):1017-29
references.pmid: 22595673
references.citation: Mol Cell. 2012 Aug 10;47(3):371-82
references.pmid: 22748924
references.citation: Nature. 2012 Sep 6;489(7414):115-20
references.pmid: 22842904
references.citation: Nat Struct Mol Biol. 2012 Sep;19(9):876-83
references.pmid: 22902369
references.citation: Dev Cell. 2012 Oct 16;23(4):745-55
references.pmid: 23079597
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18419-24
references.pmid: 23091007
references.citation: J Cell Biol. 2013 Apr 15;201(2):177-89
references.pmid: 23589490
references.citation: Trends Biochem Sci. 2013 Jun;38(6):302-11
references.pmid: 23598156
references.citation: Mol Biol Cell. 2014 Mar;25(5):594-605
references.pmid: 24403607
references.citation: Mol Cell. 2014 Jan 23;53(2):179-92
references.pmid: 24462202
references.citation: Cell. 2014 May 8;157(4):910-21
references.pmid: 24813613
references.citation: Cell. 2014 Jun 19;157(7):1671-84
references.pmid: 24949976
references.citation: Nature. 2014 Sep 18;513(7518):388-393
references.pmid: 25043029
references.citation: Curr Opin Struct Biol. 2014 Dec;29:1-9
references.pmid: 25174288
references.citation: Nat Rev Mol Cell Biol. 2014 Nov;15(11):736-47
references.pmid: 25303117
references.citation: Mol Cell. 2014 Oct 23;56(2):232-245
references.pmid: 25306918
references.citation: Mol Cell. 2014 Oct 23;56(2):246-260
references.pmid: 25306923
references.citation: Nat Cell Biol. 2014 Dec;16(12):1257-64
references.pmid: 25402682
references.citation: Nat Rev Mol Cell Biol. 2015 Feb;16(2):82-94
references.pmid: 25604195
references.citation: Dev Cell. 2015 Feb 9;32(3):358-372
references.pmid: 25669885
references.citation: Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5272-9
references.pmid: 25825779
references.citation: Science. 2015 Apr 10;348(6231):1248737
references.pmid: 25859049
references.citation: Nat Rev Mol Cell Biol. 2015 Aug;16(8):473-85
references.pmid: 26204159
references.citation: Nature. 2015 Sep 24;525(7570):523-7
references.pmid: 26399832
references.citation: Mol Biol Cell. 2015 Dec 1;26(24):4325-32
references.pmid: 26446837
references.citation: Nat Commun. 2016 Feb 25;7:10818
references.pmid: 26912231
references.citation: Curr Biol. 1996 Apr 1;6(4):455-66
references.pmid: 8723350