Regulation of the ubiquitin-ligase complex APC/C by XErp1 (B01)

这个项目的首要目标是了解翻译后蛋白质修饰和蛋白质破坏的相互作用如何调节细胞周期进程。具体来说，我们将调查逮捕未成熟非洲爪蟾卵母细胞减数分裂前期的分子机制，以及如何激素诱导释放从这个逮捕。一个特别的重点将是泛素连接酶APC/C和蛋白激酶PKA。来自不同生物体的研究表明，APC/C对于未成熟卵母细胞的prophase-I停滞是重要的。然而，它在维持第一预言逮捕的确切功能还没有得到很好的理解。PKA的活性似乎也是阻止未成熟卵母细胞在前体蛋白酶-I的关键。然而，相关目标以及PKA如何调节其活动在很大程度上仍然难以捉摸。我们希望我们的研究将提供重要的见解调节减数分裂细胞周期的机制，从而扩大我们的一般理解的机制，适用于生物系统，以适应其蛋白质组的功能，以满足特定的需求。

The overarching aim of this project is to understand how the interplay of posttranslational protein modifications and protein destruction regulates cell cycle progression. Specifically, we will investigate the molecular mechanisms underlying the arrest of immature Xenopus laevis oocytes in prophase of meiosis I and how hormone induces the release from this arrest. A particular focus will be on the ubiquitin ligase APC/C and the protein kinase PKA. Studies from different organisms indicate that the APC/C is important for the prophase-I arrest of immature oocytes. However, its precise function in maintaining the prophase-I arrest is not well understood. The activity of PKA seems also to be critical for the arrest of immature oocytes at prophase-I. However, the relevant targets and how PKA regulates their activities remains largely elusive. We expect that our studies will provide important insights into the mechanisms regulating the meiotic cell cycle and thereby broaden our general understanding of the mechanisms applied by biological systems to adapt the functionality of their proteome to specific needs.