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

该项目的总体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，我们将研究非洲爪蟾未成熟卵母细胞在减数分裂I前期阻滞的分子机制，以及激素如何诱导这种阻滞的释放。我们将特别关注泛素连接酶APC/C和蛋白激酶PKA。来自不同生物的研究表明，APC/C对未成熟卵母细胞的前期i期阻滞很重要。然而，它在维持前驱i期阻滞中的确切功能尚不清楚。PKA的活性似乎也对未成熟卵母细胞在前期i期的阻滞至关重要。然而，相关的靶标以及PKA如何调节它们的活动在很大程度上仍然是难以捉摸的。我们期望我们的研究将为减数分裂细胞周期的调节机制提供重要的见解，从而扩大我们对生物系统应用于适应其蛋白质组功能以满足特定需求的机制的一般理解。

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.