Proteasomes in apoptosis: villains or guardians?
The proteasome (multicatalytic proteinase complex, prosome) is a major cytoplasmic proteolytic enzyme, responsible for degradation of the vast majority of intracellular proteins. Proteins degraded by the proteasome are usually tagged with multiple ubiquitin moieties, conjugated to the substrates by a complicated cascade of enzymes. Over the last years, evidence has accumulated that changes in the expression and activity of the different components of the ubiquitin-proteasome system occur during apoptosis. Proteasome inhibitors have been used to induce apoptosis in various cell types, whereas in others, these compounds were able to prevent apoptosis induced by different stimuli. The proteasome mediated step(s) in apoptosis is located upstream of mitochondrial changes and caspase activation, and can involve in different systems Bcl-2, Jun N-terminal kinase, heat shock proteins, Myc, p53, polyamines and other factors.
Wójcik
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Department of Histology and Embryology, Institute of Biostructure, Medical University of Warsaw, Warszawa, Poland. cwojcik@ib.amwaw.edu.pl
D000818:Animals; D017209:Apoptosis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D007313:Insecta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
D009097:Multienzyme Complexes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex