Functional characterization of human proapoptotic molecules in yeast S. cerevisiae.
The presence of a complete (BH1-3) proapoptotic molecule is necessary for the induction of the intrinsic apoptotic cascade in mammalian cells. It is unclear, however, what distinct roles the members of the large family of BH3-only proapoptotic molecules play in apoptosis. Although biochemical analysis of these molecules can characterize binding efficiencies of BH3 family members, the biologic consequences of these interactions are difficult to predict. We have, therefore, established three functional categories of BH3-only human proapoptotic proteins based on their toxicity after expression in budding yeast: directly killing (tBid), sensitizing in Bax/Bcl-2 expressing cells (Bad or Puma), and non-toxic (BNip3, BNip3L, and Noxa). The mechanism of killing by the proapoptotic molecules in yeast, however, is not due to activation of the recently described yeast metacaspase MCA1.
Guscetti
Franco
F
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nath
Nandita
N
Denko
Nicholas
N
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology / Q000633:toxicity; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology / Q000633:toxicity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology / Q000633:toxicity; D051028:bcl-2-Associated X Protein
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein