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EMBO Rep. 2018 Oct 29. pii: e46433. doi: 10.15252/embr.201846433. [Epub ahead of print]

Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20.

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Department of Biology, University of Konstanz, Konstanz, Germany.
Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
MRC Laboratory of Molecular Biology, Cambridge, UK.
Department of Biology, University of Konstanz, Konstanz, Germany


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/CC dc20 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/CC dc20 activation. Here, we discover that CaN contributes to APC/CC dc20 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.


Xenopus laevis ; APC/C; Calcineurin; Cdc20; Meiosis; XErp1


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