Unraveling the interplay between PKA inhibition and Cdk1 activation during oocyte meiotic maturation.

Oocytes are arrested in prophase I. In vertebrates, meiotic resumption is triggered by hormonal stimulation that results in cAMP-dependent protein kinase (PKA) downregulation leading to Cdk1 activation. Yet the pathways connecting PKA to Cdk1 remain unclear. Here, we identify molecular events triggered by PKA downregulation occurring upstream of Cdk1 activation. We describe a two-step regulation controlling cyclin B1 and Mos accumulation, which depends on both translation and stabilization. Cyclin B1 accumulation is triggered by PKA inhibition upstream of Cdk1 activation, while its translation requires Cdk1 activity. Conversely, Mos translation initiates in response to the hormone, but the protein accumulates only downstream of Cdk1. Furthermore, two successive translation waves take place, the first controlled by PKA inhibition and the second by Cdk1 activation. Notably, Arpp19, an essential PKA effector, does not regulate the early PKA-dependent events. This study elucidates how PKA downregulation orchestrates multiple pathways that converge toward Cdk1 activation and induce the oocyte G2/M transition. [Display omitted] • Multiple molecular pathways connect PKA downregulation to Cdk1 activation • Cyclin B1 and Mos accumulation is opposingly controlled by a two-step mechanism • Two waves of translation occur during the G2/M transition Santoni et al. identify multiple pathways connecting PKA downregulation to Cdk1 activation and controlling G2/M transition in oocytes. Among the events taking place upstream of Cdk1 activation, they highlight the interplay between protein translation and stabilization in controlling the accumulation of critical cell-cycle regulators, including Mos and cyclin B1. [ABSTRACT FROM AUTHOR]