FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMES

描述(摘自申请人的摘要)：泛素与赖氨酸的偶联 细胞蛋白质的残基是降解的共价信号 26S水解酶。泛素在降解过程中被循环利用 泛素-底物(或泛素-泛素)异肽的切割 邦德(S)。一个令人惊讶的脱泛素酶家族 (异肽酶)目前已知存在，其中包括S。 酿酒。尽管很明显存在一些功能重叠 在这个家庭的某些成员中，很明显，其他人执行 相对选择性的功能。这项建议主要集中在两个方面 后一类酶，DoA4和UBP14(Iso T)。这些酶是 建议在26S的最后阶段扮演不同的、顺序的角色 蛋白酶介导的降解。一种生化和遗传的结合 将采取方法来检验关于结构的具体假设 以及每种酶的功能。调查结果将为我们提供对 泛素结合物的降解机制，并可能降解为 许多脱泛素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.