SPECIAL SEMINAR
Professor Eric Strieter
University of Wisconsin-Madison
“Dissecting the functions of deubiquitinases using chemical tools”
Thursday, January 28th
11:00 AM
Chemistry Room #1315
The human genome encodes approximately 100 deubiquitinating enzymes (also known as DUBs). These
enzymes regulate a broad swath of cell and organismal biology by removing the small protein ubiquitin (Ub)
from target proteins or trimming Ub oligomers. Despite the importance of DUBs, there are fundamental
gaps in our knowledge regarding how they work. The family of DUBs known as the Ub C-terminal
hydrolases (UCHs) embodies this situation. Biochemical data suggests UCHs catalyze the removal of small
C-terminal adducts from Ub, whereas data from cellular studies implicates these enzymes in the
disassembly of Ub oligomers. Recently, our laboratory developed a straightforward chemical approach
towards the synthesis of a wide array of ubiquitin oligomers. Using these oligomers to probe the function of
DUBs, we discovered two members of the UCH family, UCH37 and UCHL3, selectively hydrolyze Ub chains
in which a single Ub subunit is modified with two Ub molecules through two lysine residues (referred to as
branched Ub chains). Considering the importance of UCHL3 and UCH37 in cellular differentiation,
development, and motility, our results suggest branched Ub chains play far more important roles in biology
than ever appreciated. In this talk, I will discuss our efforts to understand the molecular details of this unique
biochemical activity.