Novel Proteasome Activators for the Study of Proteasome Population Dynamics and MHC-I Peptide Generation

Abstract

The 26S proteasome is the major protease found in eukaryotic cells. It is responsible for the degradation of most proteins into a mixture of heterogeneous small peptides. Proteasomes are tightly regulated, relying on ubiquitin tagging for substrate loading and ATP hydrolysis for protein degradation. A number of proteasome activators have been previously described. Here, I show that the UBL domain of Rad23a is a potent activator of the double-capped and single-capped 26S proteasome but an inhibitor of the 20S. Additionally, peptide presentation by MHC-I increases with heat shock, which also activates proteasomes.