A novel role for a familiar protein in apoptosis induced by proteasome inhibition.
In this issue of Cancer Cell, Nickeleit et al. (2008) identify a new proteasome inhibitor, argyrin A, and show that it induces apoptosis and inhibits angiogenesis via p27-dependent mechanisms. Their observations challenge current thinking about how this class of promising cancer therapies works and why they selectively kill cancer cells.
McConkey
David J
DJ
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. dmcconke@mdanderson.org
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009336:Necrosis; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
D020533:Angiogenesis Inhibitors; D001897:Boronic Acids; C436291:CDKN1B protein, human; D015853:Cysteine Proteinase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex