Activity-Based Ubiquitin Probes for Investigation of Deubiquitinases

Gui, Weijun; Paudel, Prajwal; Zhuang, Zhihao

Abstract Ubiquitination is emerging as an important post-translational modification (PTM) for numerous cellular functions including protein degradation, DNA damage repair and tolerance, and cell cycle progression. Compared with other small-molecule modifiers found in phosphorylation, acetylation and glycosylation, ubiquitin is a small protein modifier that exists as either a single ubiquitin or a polyubiquitin chain. Furthermore, the polyubiquitin chains are formed via various linkages imparting an additional layer of specificity in cellular signaling. In order to adequately study ubiquitin signaling and particularly deubiquitination, a number of ubiquitin activity-based probes (ABPs) were developed and utilized in understanding the deubiquitinase (DUBs) function. Here, we focus on the current state of the DUB ABP development and their application in understanding DUB function and specificity for polyubiquitin chains and ubiquitinated proteins.