Maintenance of G(2) arrest in the Xenopus oocyte: a role for 14-3-3-mediated inhibition of Cdc25 nuclear import

Cdc2-cyclin B1 in the G(2)-arrested Xenopus oocyte is held inactive by phos phorylation of Cdc2 at two negative regulatory sites, Thr14 and Tyr15. Upon treatment with progesterone, these sites are dephosphorylated by the dual specificity phosphatase, Cdc25, leading to Cdc2-cyclin B1 activation. Where as maintenance of the G(2) arrest depends upon preventing Cdc25-induced Cdc 2 dephosphorylation, the mechanisms responsible for keeping Cdc25 in check in these cells have not yet been described. Here we report that Cdc25 in th e G(2)-arrested oocyte is bound to 14-3-3 proteins and that progesterone tr eatment abrogates this binding. We demonstrate that Cdc25, apparently stati cally localized in the cytoplasm, is actually capable of shuttling in and o ut of the oocyte nucleus. Binding of 14-3-3 protein markedly reduces the nu clear import rate of Cdc25, allowing nuclear export mediated by a nuclear e xport sequence present in the N-terminus of Cdc25 to predominate. If 14-3-3 binding to Cdc25 is prevented while nuclear export is inhibited, the coord inate nuclear accumulation of Cdc25 and Cdc2-cyclin B1 facilitates their mu tual activation, thereby promoting oocyte maturation.