title: SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression.
abstract: Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCF(β-TRCP) reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCF(β-TRCP). Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions.
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors: Hidefumi
authors: H
authors: Fukushima
authors: Kohei
authors: K
authors: Ogura
authors: Lixin
authors: L
authors: Wan
authors: Ying
authors: Y
authors: Lu
authors: Victor
authors: V
authors: Li
authors: Daming
authors: D
authors: Gao
authors: Pengda
authors: P
authors: Liu
authors: Alan W
authors: AW
authors: Lau
authors: Tao
authors: T
authors: Wu
authors: Marc W
authors: MW
authors: Kirschner
authors: Hiroyuki
authors: H
authors: Inuzuka
authors: Wenyi
authors: W
authors: Wei
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism; D000818:Animals; D064200:Cdh1 Proteins / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism; D025461:Feedback, Physiological; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D014981:Xenopus; D000097869:Polo-Like Kinase 1
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D044843:SKP Cullin F-Box Protein Ligases; D000097869:Polo-Like Kinase 1
references: Nature. 1999 Oct 21;401(6755):815-8
references: 10548110
references: FEBS J. 2010 Jan;277(2):357-67
references: 20015233
references: Nat Rev Mol Cell Biol. 2004 Sep;5(9):739-51
references: 15340381
references: Nature. 2009 Aug 27;460(7259):1132-5
references: 19668191
references: Carcinogenesis. 2008 Feb;29(2):263-72
references: 18174259
references: Mol Biol Cell. 2009 Jul;20(14):3305-16
references: 19477924
references: FEBS Lett. 2011 Sep 16;585(18):2803-9
references: 21624367
references: Mol Cell. 2011 Oct 21;44(2):290-303
references: 22017875
references: Mol Cell. 2010 Sep 10;39(5):797-808
references: 20832730
references: Oncogene. 2002 Jan 24;21(5):856-60
references: 11850814
references: Mol Cell. 2002 May;9(5):931-43
references: 12049731
references: EMBO J. 2004 Apr 7;23(7):1619-26
references: 15029244
references: Nature. 2004 Mar 11;428(6979):190-3
references: 15014502
references: Genes Dev. 2002 Sep 1;16(17):2179-206
references: 12208841
references: Cell Signal. 2009 Jan;21(1):43-51
references: 18929646
references: Methods Cell Biol. 1991;36:657-62
references: 1811156
references: Cell. 2003 Oct 3;115(1):83-95
references: 14532005
references: Genes Dev. 2006 Sep 1;20(17):2410-20
references: 16921029
references: Cell Res. 2013 Jul;23(7):947-61
references: 23670162
references: Mol Cell Biol. 2000 Oct;20(20):7613-23
references: 11003657
references: Mol Cell. 2011 Dec 9;44(5):721-33
references: 22152476
references: Mol Cell Biol. 2001 Mar;21(6):2192-202
references: 11238952
references: Biochem Biophys Res Commun. 2001 Apr 13;282(4):853-60
references: 11352628
references: Nat Cell Biol. 2006 Oct;8(10):1095-101
references: 16980960
references: Cell Cycle. 2005 Sep;4(9):1230-2
references: 16123585
references: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):33-8
references: 16371461
references: J Cell Biol. 2007 Jul 30;178(3):371-85
references: 17664332
references: Semin Cell Dev Biol. 2005 Jun;16(3):323-33
references: 15840441
references: Oncogene. 2004 Mar 15;23(11):2028-36
references: 15021890
references: Cell. 2010 Apr 16;141(2):268-79
references: 20403323
references: Nature. 2006 Sep 28;443(7110):421-6
references: 16957735
references: Genes Dev. 2007 Dec 15;21(24):3214-31
references: 18079171
references: Cancer Cell. 2010 Aug 9;18(2):147-59
references: 20708156
references: Cell Stem Cell. 2007 Jun 7;1(1):87-99
references: 18371338
references: Mol Biol Cell. 2010 Mar 15;21(6):914-25
references: 20089834
references: Genes Dev. 2003 Dec 15;17(24):3062-74
references: 14681206
references: Nat Cell Biol. 2002 May;4(5):358-66
references: 11988738
references: Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
references: 16896351
references: Nature. 2004 Mar 11;428(6979):194-8
references: 15014503
references: J Biol Chem. 2003 Jul 11;278(28):25277-80
references: 12738781
references: Science. 2003 Feb 21;299(5610):1228-31
references: 12595692
references: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
references: 18669648
references: Mol Cell Biol. 2001 Jun;21(11):3692-703
references: 11340163
references: J Biol Chem. 2001 Jul 20;276(29):27152-8
references: 11375388
references: Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20
references: 15688063
references: Curr Biol. 2007 Feb 20;17(4):316-22
references: 17291758
references: Development. 1998 Aug;125(16):3247-58
references: 9671596
references: Nature. 2002 Aug 1;418(6897):556-62
references: 12152084
references: Nat Cell Biol. 2009 Apr;11(4):397-408
references: 19270695
references: Cell Cycle. 2010 Jun 15;9(12):2342-52
references: 20519948
references: Mol Cell Biol. 2005 Aug;25(15):6464-74
references: 16024784