Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma.
Multiple mechanisms are likely to be involved, but proteasome inhibition may prevent degradation of pro-apoptotic factors such as the p53 protein, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. For example, bortezomib causes a rapid and dramatic change in the levels of intracellular peptides.
Skeletal muscle proteolysis is increased in catabolic states such as fasting, immobilization, aging, and disease . HMB has been shown to decrease skeletal muscle protein degradation both in vitro[72,73] and in vivo. ... Indeed, HMB has been shown to decrease proteasome expression  and activity [72,78-80] during catabolic states, thus attenuating skeletal muscle protein degradation through the ubiquitin-proteasome pathway.
HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass.
although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ∼50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).[permanent dead link]