Abstract
The promising effects of the proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of certain types of cancer have fired up the interest on this multicatalytic proteolytic machinery. A number of recent reviews thoroughly describe various aspects of the ubiquitin-proteasome system and its importance in the control of cell growth and tumorigenesis. Here, we will focus on recent data unveiling a link between the proteasome and some elements of the apoptotic machinery including Bcl-2 members, caspases, IAPs and IAP antagonists. Perturbing their turnover significantly contributes to the apoptotic response and the anti-neoplastic activity of proteasome inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis Regulatory Proteins
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Apoptosis*
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Boronic Acids / pharmacology
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Boronic Acids / therapeutic use
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Bortezomib
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Caspases / metabolism
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Drug Resistance, Neoplasm
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Humans
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Inhibitor of Apoptosis Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Mitochondria / drug effects
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Mitochondria / enzymology
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Mitochondrial Proteins / metabolism
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Neoplasm Proteins / metabolism*
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Protease Inhibitors / pharmacology*
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Protease Inhibitors / therapeutic use
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Pyrazines / pharmacology
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Pyrazines / therapeutic use
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Receptors, Tumor Necrosis Factor / drug effects
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Receptors, Tumor Necrosis Factor / metabolism
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligases / metabolism
Substances
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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Boronic Acids
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DIABLO protein, human
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Mitochondrial Proteins
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Neoplasm Proteins
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Protease Inhibitors
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Proteasome Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Pyrazines
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Receptors, Tumor Necrosis Factor
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Ubiquitin
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Bortezomib
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Ubiquitin-Protein Ligases
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Caspases
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Proteasome Endopeptidase Complex