Neither macromolecular synthesis nor myc is required for cell death via the mechanism that can be controlled by Bcl-2.
Expression of c-myc and macromolecular synthesis have been associated with physiological cell death. We have studied their requirement for the death of factor (interleukin-3)-dependent cells (FDC-P1) bearing an inducible bcl-2 expression construct. FDC-P1 cells expressing bcl-2 turned off expression of c-myc when deprived of interleukin-3 but remained viable as long as bcl-2 was maintained. A subsequent decline in Bcl-2 allowed the cells to undergo apoptosis directly from G0, in the absence of detectable c-myc expression. Thus c-myc expression may lead to apoptosis in some cases but is not directly involved in the mechanism of physiological cell death that can be controlled by Bcl-2. The macromolecular synthesis inhibitors actinomycin D and cycloheximide triggered rapid cell death of FDC-P1 cells in the presence of interleukin-3, but the cells could be protected by Bcl-2. Thus, the cell death machinery can exist in a quiescent state and can be activated by mechanisms that do not require synthesis of RNA or protein.
Vaux
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DL
Department of Pathology, Stanford University Medical Center, California 94305.
Weissman
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IL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015152:Blotting, Northern; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression; D016259:Genes, myc; D006412:Hematopoietic Stem Cells; D006801:Humans; D007700:Kinetics; D011061:Poly A / Q000096:biosynthesis / Q000302:isolation & purification; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011519:Proto-Oncogenes; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D014162:Transfection
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003609:Dactinomycin; D011061:Poly A; D012313:RNA; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases