title: Hec1-dependent cyclin B2 stabilization regulates the G2-M transition and early prometaphase in mouse oocytes.
abstract: The functions of the Ndc80/Hec1 subunit of the highly conserved Ndc80 kinetochore complex are normally restricted to M phase when it exerts a pivotal kinetochore-based role. Here, we find that in mouse oocytes, depletion of Hec1 severely compromises the G2-M transition because of impaired activation of cyclin-dependent kinase 1 (Cdk1). Unexpectedly, impaired M phase entry is due to instability of the Cdk1-activating subunit, cyclin B2, which cannot be covered by cyclin B1. Hec1 protects cyclin B2 from destruction by the Cdh1-activated anaphase-promoting complex (APC(Cdh1)) and remains important for cyclin B2 stabilization during early M phase, required for the initial stages of acentrosomal spindle assembly. By late M phase, however, Hec1 and cyclin B2 become uncoupled, and although Hec1 remains stable, APC(Cdc20) triggers cyclin B2 destruction. These data identify another dimension to Hec1 function centered on M phase entry and early prometaphase progression and challenge the view that cyclin B2 is completely dispensable in mammals.
authors.affiliation: Mammalian Oocyte and Embryo Research Laboratory, Cell and Developmental Biology, UCL, London WC1E 6BT, UK.
authors.forename: Liming
authors.initials: L
authors.lastname: Gui
authors.forename: Hayden
authors.initials: H
authors.lastname: Homer
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D056765:Cyclin B2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D008677:Metaphase; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D049468:Prometaphase; D011418:Prophase; D055550:Protein Stability; D059748:Proteolysis; D064249:Securin; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C503759:Ccnb2 protein, mouse; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D056765:Cyclin B2; C577585:Fzr1 protein, mouse; C533103:Hec1 protein, mouse; D008869:Microtubule-Associated Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome
references.citation: Microsc Microanal. 2011 Jun;17(3):431-9
references.pmid: 21600073
references.citation: J Biol Chem. 2010 Jun 11;285(24):18291-300
references.pmid: 20404349
references.citation: Mol Cell. 2010 May 14;38(3):383-92
references.pmid: 20471944
references.citation: Curr Biol. 2008 Nov 25;18(22):1778-84
references.pmid: 19026543
references.citation: Science. 2011 Apr 22;332(6028):462-5
references.pmid: 21454751
references.citation: J Cell Sci. 2011 Feb 15;124(Pt 4):622-34
references.pmid: 21266467
references.citation: PLoS One. 2007 Nov 28;2(11):e1165
references.pmid: 18043727
references.citation: Cell. 2008 May 2;133(3):427-39
references.pmid: 18455984
references.citation: Mol Biol Cell. 2005 Feb;16(2):519-31
references.pmid: 15548592
references.citation: Cell. 2007 Aug 10;130(3):484-98
references.pmid: 17693257
references.citation: Dev Biol. 2001 Apr 15;232(2):400-13
references.pmid: 11401401
references.citation: Mol Biol Cell. 2005 May;16(5):2325-38
references.pmid: 15728720
references.citation: Mol Biol Cell. 2009 Nov;20(22):4686-95
references.pmid: 19776357
references.citation: Science. 2002 Sep 27;297(5590):2267-70
references.pmid: 12351790
references.citation: Curr Biol. 2009 Mar 10;19(5):369-80
references.pmid: 19249208
references.citation: Curr Biol. 2003 Dec 2;13(23):2103-9
references.pmid: 14654001
references.citation: Oncogene. 2007 Nov 8;26(51):7175-84
references.pmid: 17533373
references.citation: Reproduction. 2005 Dec;130(6):829-43
references.pmid: 16322543
references.citation: Cytogenet Genome Res. 2011;133(2-4):209-22
references.pmid: 21335952
references.citation: J Cell Biol. 2007 Jan 1;176(1):65-75
references.pmid: 17190794
references.citation: Mol Biol Cell. 2011 Mar 15;22(6):759-68
references.pmid: 21270439
references.citation: Nat Cell Biol. 2008 Apr;10(4):445-51
references.pmid: 18364698
references.citation: PLoS Genet. 2010 Sep 30;6(9):e1001147
references.pmid: 20941357
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16719-24
references.pmid: 18940925
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4344-9
references.pmid: 9539739
references.citation: Development. 2010 Apr;137(8):1297-304
references.pmid: 20223764
references.citation: J Biol Chem. 1997 Sep 19;272(38):24081-7
references.pmid: 9295362
references.citation: Curr Biol. 2007 Jan 9;17(1):85-91
references.pmid: 17208191
references.citation: Cell Prolif. 2011 Feb;44(1):1-9
references.pmid: 21199005
references.citation: Nature. 2007 Nov 29;450(7170):745-9
references.pmid: 18046416
references.citation: FEBS Lett. 2007 Jun 19;581(15):2862-9
references.pmid: 17521635
references.citation: Biol Reprod. 2009 Apr;80(4):795-803
references.pmid: 19129509
references.citation: Elife. 2012 Dec 18;1:e00117
references.pmid: 23275833
references.citation: Cell. 2011 Aug 19;146(4):568-81
references.pmid: 21854982
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):E1858-67
references.pmid: 22552228
references.citation: J Cell Biol. 2010 Dec 27;191(7):1251-60
references.pmid: 21173113
references.citation: Biol Reprod. 2009 Oct;81(4):768-76
references.pmid: 19553597
references.citation: Development. 1993 May;118(1):229-40
references.pmid: 8375336
references.citation: Curr Biol. 2008 Nov 25;18(22):1785-91
references.pmid: 19026542
references.citation: Nat Cell Biol. 2006 May;8(5):539-40
references.pmid: 16715549
references.citation: Cell. 2006 Dec 1;127(5):969-82
references.pmid: 17129782
references.citation: Development. 2012 Jun;139(11):1941-6
references.pmid: 22513372
references.citation: Nat Struct Mol Biol. 2007 Jan;14(1):54-9
references.pmid: 17195848
references.citation: Genes Dev. 2005 Jan 15;19(2):202-7
references.pmid: 15655110
references.citation: J Cell Sci. 2003 Aug 15;116(Pt 16):3347-62
references.pmid: 12829748
references.citation: PLoS One. 2008 Oct 03;3(10):e3338
references.pmid: 18833336
references.citation: EMBO J. 1993 Oct;12(10):3773-8
references.pmid: 8404848
references.citation: Nat Cell Biol. 2007 Oct;9(10):1192-8
references.pmid: 17891138
references.citation: Science. 2009 Nov 13;326(5955):991-4
references.pmid: 19965510