Regulation of MBK-2/DYRK during the oocyte-to-embryo transition.

摘要

Oocyte-to-embryo transition marks the beginning of embryonic development and is a tightly regulated process that converts an egg to a totipotent zygote. In C. elegans, MBK-2 is essential for this transition. MBK-2 phosphorylates some oocyte proteins (e.g. MEI-1 and OMA-1) at the end of meiosis to promote their degradation. MBK-2 belongs to the dual specificity tyrosine-regulated kinase (DYRK) family, which has been shown to play important roles in many cellular processes, but the regulatory mechanism of MBK-2/DYRK kinases is still poorly understood. In this thesis study, we provide three distinct molecular mechanisms for how MBK-2/DYRK is regulated. Specifically, we demonstrate that during oocyte maturation, MBK-2 is activated by CDK-1-dependent phosphorylation and its kinase activity is temporally inhibited by two pseudo-phosphatases, EGG-4 and EGG-5. We also show that MBK-2 can be negatively regulated by its subcellular localization. The anti-phosphatase, EGG-3 that tethers MBK-2 on the cortex until late meiosis, prevents MBK-2 from reaching its target too early during the oocyte-to-embryo transition. Our findings provide new insights into the regulation of MBK-2/DRYK kinases and the oocyte-to-embryo transition.