SUMOylation regulates germinal vesicle breakdown and the Akt/PKB pathway during mouse oocyte maturation.

SUMOylation, a process of posttranslational modification of proteins by the small ubiquitin-related modifier (SUMO) family of proteins, is known to be involved in yeast and mammalian somatic cell-cycle regulation. However, the identities of the SUMO-modified oocyte targets are largely unknown and the functional role(s) for SUMOylation during mammalian oocyte maturation remains unclear. On the basis of studies in non-germline cells, protein kinase B/Akt is a potential SUMOylation target in the mouse oocyte, where it plays an essential role in cell-cycle resumption and progression during maturation. This study investigated the temporal patterns and prospective role(s) for interactions between SUMOylation and Akt serine-phosphorylation during oocyte meiotic resumption. Pharmacological inhibition of SUMOylation significantly decreased follicular fluid meiosis-activating sterol-induced cell-cycle resumption in oocytes matured in vitro and negatively affected the phosphorylation and nuclear translocation of Akt. Similarly, nuclear localization of cyclin D1, a downstream target of Akt activation, was significantly decreased following SUMOylation inhibition. Together these data show that SUMO and the posttranslational process of SUMOylation are involved in cell-cycle resumption during murine oocyte maturation and exert a regulatory influence on the Akt pathway during germinal vesicle breakdown.