Proteasomes in apoptosis: villains or guardians?

The proteasome (multicatalytic proteinase complex, prosome) is a major cyto plasmic proteolytic enzyme, responsible for degradation of the vast majorit y of intracellular proteins. Proteins degraded by the proteasome are usuall y tagged with multiple ubiquitin moieties, conjugated to the substrates by a complicated cascade of enzymes. Over the last years, evidence has accumul ated that changes in the expression and activity of the different component s of the ubiquitin-proteasome system occur during apoptosis. Proteasome inh ibitors have been used to induce apoptosis in various cell types, whereas i n others, these compounds were able to prevent apoptosis induced by differe nt stimuli. The proteasome mediated step(s) in apoptosis is located upstrea m of mitochondrial changes and caspase activation, and can involve in diffe rent systems Bcl-2, Jun N-terminal kinase, heat shock proteins, Myc, p53, p olyamines and other factors.