FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMES

描述（来自申请人摘要）：泛素与赖氨酸的缀合 细胞蛋白质的残基是一个共价信号，用于降解， 26 S蛋白酶。 泛素在降解过程中通过以下方式再循环： 泛素-底物（或泛素-泛素）异肽的切割 债券 一个令人惊讶的大家族的去泛素化酶 （isopeptidases），包括17个成员。 啤酒。 虽然很明显存在一些职能重叠 在这个家庭的某些成员中，很明显， 相对选择性的功能。 这一建议主要集中在两个方面 后一种类型的酶，Doa 4和UBP 14（iso T）。 这些酶 建议在26 S的最后阶段发挥不同的、顺序的作用 蛋白酶介导的降解。 生物化学和遗传学相结合 将采取一种方法来检验关于结构的具体假设 每种酶的功能。 结果将提供深入了解 泛素结合物的降解机制，并可能进入 许多去泛素化酶存在的生物学原理。

DESCRIPTION (From applicant's abstract): Conjugation of ubiquitin to Lys residues of cellular proteins is a covalent signal for degradation by the 26S protease. Ubiquitin is recycled during the degradative process by cleavage of the ubiquitin-substrate (or ubiquitin-ubiquitin) isopeptide bond(s). A surprisingly large family of deubiquitinating enzymes (isopeptidases) is now known to exist, including 17 members in S. cerevisiae. Although it is clear that some functional overlap exists among certain members of this family, it is evident that others carry out relatively selective functions. This proposal focuses mainly on two enzymes of the latter type, Doa4 and UBP14(iso T). These enzymes are proposed to play distinct, sequential roles in the final stages of 26S protease-mediated degradation. A combined biochemical and genetic approach will be taken to test specific hypotheses about the structure and function of each enzyme. The results will provide insight into the mechanism of degradation of ubiquitin conjugates, and possibly into the biological rationale for the existence of many deubiquitinating enzymes.