Studying atypical ubiquitin chains with deubiquitinases (353.2)

Abstract

Polyubiquitin chains can be assembled in multiple ways via eight different linkage points on ubiquitin. Single‐linkage homotypic chains but also heterotypic chains with branched or mixed linkage types regulate many aspects of the ubiquitin system, however we lack methods to study different polyubiquitin chains.We recently discovered high intrinsic linkage‐specificity in OTU domain deubiquitinases, which have evolved specific members for most ubiquitin chain types, such as the Lys11‐specific DUB Cezanne, the Met1‐specific DUB OTULIN and the Lys6/Lys11‐specific enzyme OTUD3. Together, these proteins enable a better understanding of mechanisms of linkage specificity and of the biology of atypical chains. Moreover, linkage‐specific DUBs can be used as tools to interrogate polyubiquitin chain architecture, and are especially useful for the analysis of mixed/branched polyubiquitin. In my talk, I will discuss our recent efforts to understand the biology of atypical ubiquitin chain types using linkage‐specific DUBs of the OTU family.