Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, 12801 E. 17th Ave, Aurora, CO 80045, USA.
Trends Biochem Sci. 2013 Feb;38(2):103-10. doi: 10.1016/j.tibs.2012.11.009. Epub 2013 Jan 2.
The 26S proteasome degrades ubiquitylated proteins. It consists of the 20S proteasome and the PA700/19S complex. PA700 plays essential roles in processing ubiquitylated substrates; it can bind, deubiquitylate, and unfold ubiquitylated proteins, which then translocate into the proteolytic chamber of the 20S proteasome for degradation. Here, we summarize the current knowledge of PA700-mediated substrate binding and deubiquitylation, and provide models to explain how substrate binding and deubiquitylation could regulate proteasomal degradation. We also discuss the features and potential therapeutic uses of the two recently identified small molecule inhibitors of the proteasome-residing deubiquitylating enzymes.
26S 蛋白酶体降解泛素化蛋白。它由 20S 蛋白酶体和 PA700/19S 复合物组成。PA700 在泛素化底物的加工中起着至关重要的作用；它可以结合、去泛素化和解折叠泛素化蛋白，然后将其转运到 20S 蛋白酶体的蛋白酶腔进行降解。在这里，我们总结了 PA700 介导的底物结合和去泛素化的最新知识，并提供了模型来解释底物结合和去泛素化如何调节蛋白酶体降解。我们还讨论了最近发现的两种蛋白酶体驻留去泛素化酶小分子抑制剂的特征和潜在治疗用途。
