Cell cycle regulation by ubiquitin ligases

描述(申请人提供)：在细胞周期转变或对外界条件变化的反应中，细胞生理的快速变化通常是由调节分子的降解所调节的。这些变化通常是通过用小蛋白泛素链修饰蛋白质靶标来实现的。泛素化是由一系列三种酶执行的，有时被称为E1、E2和E3，它们的功能是将泛素转移到底物上。底物特异性通常由E3复合体介导，也称为泛素连接酶。SCF和APC是两个高度保守的多亚基泛素连接酶，对细胞周期进程和细胞生理的许多方面的调节都很重要。我们将研究APC的调节机制，并使用我们最近开发的生物化学技术鉴定其他泛素连接酶的底物。最后，我们将更详细地研究泛素连接酶底物G1周期蛋白的周转。

DESCRIPTION (provided by applicant): Rapid changes in cell physiology during cell cycle transitions or in response to changes in external conditions are often mediated by the degradation of regulatory molecules. These changes are typically directed by the modification of protein targets with chains of the small protein ubiquitin. Ubiquitinization is carried out by a series of three enzymes, sometimes referred to as E1, E2 and E3, which function in tandem to transfer ubiquitin to a substrate. Substrate specificity is usually mediated by the E3 complex, also called an ubiquitin ligase. The SCF and the APC represent two highly conserved multi-subunit ubiquitin ligases important for both cell cycle progression and the regulation of many aspects of cellular physiology. We will examine mechanisms of APC regulation, and also identify the substrates other ubiquitin ligases using a biochemical technique that we have recently developed. Finally, we will explore the turnover of one ubiquitin ligase substrate, a G1 cyclin, in greater detail.