Proteasome DUBstep

Karolinska Institute researchers have identified a small molecule proteasome inhibitor for cancer that has a distinct mechanism from other compounds in the class.¹ Vivolux AB has licensed the candidate, which blocks two proteasome-associated deubiquitinating enzymes, and is performing lead optimization.

Ubiquitin ligases and deubiquitinating enzymes (DUBs) act in concert with the proteasome to maintain cellular protein homeostasis. Ligases covalently link ubiquitin to protein substrates and direct them to the proteasome for degradation. DUBs reverse this process by removing ubiquitins, and a subset of proteasome-associated DUBs aid in protein digestion by the proteasome...