Comparative Selectivity and Specificity of the Proteasome Inhibitors BzLLLCOCHO, PS-341, and MG-132

摘要: The 26S proteasome is a multicatalytic protease responsible for regulated intracellular protein degradation. Its function mediated by three main catalytic activities: (a) chymotrypsin-like (CT-L), (b) trypsin-like, and (c) peptidylglutamyl peptide hydrolysing (PGPH). Proteasome inhibition an emerging therapy many cancers novel treatment multiple myeloma. Here, we profile the contributions of activities in myeloma cell lines compare specificity cytotoxicity inhibitor BzLLLCOCHO inhibitors PS-341 (Velcade, bortezomib) MG-132. Using fluorogenic substrates active site-directed probe specific subunits, show differential subunit each inhibitors. Addition strongly inhibited all activities, with completely CT-L PGPH MG-132 resulted weak activities. Multiple cells were more sensitive to induction apoptosis than BzLLLCOCHO. This study emphasizes need further investigation effects these compounds on gene expression allow development targeted