Altering protein turnover in tumor cells: new opportunities for anti-cancer therapies.
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.
Demarchi
Francesca
F
LNICB, Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, Pardiciano 99, 34100 Trieste, Italy.
Brancolini
Claudio
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D018124:Receptors, Tumor Necrosis Factor; D025801:Ubiquitin; D000069286:Bortezomib; D044767:Ubiquitin-Protein Ligases; D020169:Caspases; D046988:Proteasome Endopeptidase Complex