For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. We are studying the multiple regulatory levels that coordinate the 20S proteasome degradation route.
In particular, we aim to reveal the intrinsic molecular switch that activates the latent 20S proteasome and identify novel proteins that bind the 20S proteasome to regulate its activity. In addition, we aim to expose the cellular cues and multiple pathways that influence 20S proteasome activity.