Nolasco-Sanchez, Jonathan2020-09-142020-052020-04-012020Nolasco-Sanchez, Jonathan. 2020. Novel Proteasome Activators for the Study of Proteasome Population Dynamics and MHC-I Peptide Generation. Master's thesis, Harvard Extension School.https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365059The 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.application/pdfProteasomeMHC-I Peptide presentationprotein degradationThesis or Dissertation2020-09-14