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EMBO Rep
2018 Dec 01;1912:. doi: 10.15252/embr.201846433.
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Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20.
Heim A
,
Tischer T
,
Mayer TU
.
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Vertebrate oocytes await fertilization arrested at metaphase of the second meiotic division. Fertilization triggers a transient calcium wave, which induces the activation of the anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdc20 resulting in the destruction of cyclin B and hence meiotic exit. Two calcium-dependent enzymes are implicated in fertilization-induced APC/CCdc20 activation: calcium-/calmodulin-dependent kinase type II (CaMKII) and calcineurin (CaN). While the role of CaMKII in targeting the APC/C inhibitor XErp1/Emi2 for destruction is well-established, it remained elusive how CaN affects APC/CCdc20 activation. Here, we discover that CaN contributes to APC/CCdc20 activation in Xenopus laevis oocytes by two independent but interrelated mechanisms. First, it facilitates the degradation of XErp1 by dephosphorylating it at a site that is part of a phosphorylation-dependent recruiting motif for PP2A-B''56, which antagonizes inhibitory phosphorylation of XErp1. Second, it dephosphorylates Cdc20 at an inhibitory site, thereby supporting its APC/C-activating function. Thus, our comprehensive analysis reveals that CaN contributes to timely APC/C activation at fertilization by both negatively regulating the APC/C inhibitory activity of XErp1 and positively regulating the APC/C-activating function of Cdc20.
Busa,
An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis.
1985, Pubmed
Busa,
An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis.
1985,
Pubmed
Cao,
CDK1 and calcineurin regulate Maskin association with eIF4E and translational control of cell cycle progression.
2006,
Pubmed
Chung,
Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint.
2003,
Pubmed
Donella-Deana,
Dephosphorylation of phosphopeptides by calcineurin (protein phosphatase 2B).
1994,
Pubmed
Fujimitsu,
Cyclin-dependent kinase 1-dependent activation of APC/C ubiquitin ligase.
2016,
Pubmed
Gerhart,
Cell cycle dynamics of an M-phase-specific cytoplasmic factor in Xenopus laevis oocytes and eggs.
1984,
Pubmed
Goldman,
The calcineurin signaling network evolves via conserved kinase-phosphatase modules that transcend substrate identity.
2014,
Pubmed
Gross,
The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk).
2000,
Pubmed
Hein,
Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.
2016,
Pubmed
Hein,
Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis.
2017,
Pubmed
Hertz,
A Conserved Motif Provides Binding Specificity to the PP2A-B56 Phosphatase.
2016,
Pubmed
Inoue,
A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs.
2007,
Pubmed
Isoda,
Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic arrest of Xenopus eggs.
2011,
Pubmed
Kinoshita,
Phosphate-binding tag, a new tool to visualize phosphorylated proteins.
2006,
Pubmed
Klee,
Calcineurin: a calcium- and calmodulin-binding protein of the nervous system.
1979,
Pubmed
Labit,
Dephosphorylation of Cdc20 is required for its C-box-dependent activation of the APC/C.
2012,
Pubmed
Li,
Cooperative autoinhibition and multi-level activation mechanisms of calcineurin.
2016,
Pubmed
Li,
Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction.
2007,
Pubmed
Lohka,
Induction of nuclear envelope breakdown, chromosome condensation, and spindle formation in cell-free extracts.
1985,
Pubmed
Lorca,
Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs.
1993,
Pubmed
Masui,
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.
1971,
Pubmed
Mochida,
Calcineurin is required to release Xenopus egg extracts from meiotic M phase.
2007,
Pubmed
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
Nishiyama,
Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis.
2007,
Pubmed
Nishiyama,
Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs.
2007,
Pubmed
Ohe,
Emi2 inhibition of the anaphase-promoting complex/cyclosome absolutely requires Emi2 binding via the C-terminal RL tail.
2010,
Pubmed
Qiao,
Mechanism of APC/CCDC20 activation by mitotic phosphorylation.
2016,
Pubmed
Rauh,
Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation.
2005,
Pubmed
Sako,
Emi2 mediates meiotic MII arrest by competitively inhibiting the binding of Ube2S to the APC/C.
2014,
Pubmed
Saneyoshi,
Molecular cloning and expression profile of Xenopus calcineurin A subunit(1).
2000,
Pubmed
Schmidt,
Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity.
2005,
Pubmed
Sheftic,
Investigating the human Calcineurin Interaction Network using the πɸLxVP SLiM.
2016,
Pubmed
Suzuki,
Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase.
2010,
Pubmed
Tang,
Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.
2010,
Pubmed
Tischer,
The APC/C inhibitor XErp1/Emi2 is essential for Xenopus early embryonic divisions.
2012,
Pubmed
Tůmová,
Calcineurin role in porcine oocyte activation.
2016,
Pubmed
Wu,
Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.
2007,
Pubmed
Yudkovsky,
Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint.
2000,
Pubmed
Zhang,
Molecular mechanism of APC/C activation by mitotic phosphorylation.
2016,
Pubmed
