Abstract
T cell hybridomas respond to activation signals by undergoing apoptotic cell death, and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo. Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis. This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here inhibits activation-induced apoptosis. Further, coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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Cell Line
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Flow Cytometry
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Humans
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Hybridomas / immunology
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Hybridomas / physiology*
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Interleukin-2 / biosynthesis
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Lymphocyte Activation / physiology*
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Macromolecular Substances
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Mutagenesis
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / metabolism*
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T-Lymphocytes / immunology*
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T-Lymphocytes / physiology
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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DNA-Binding Proteins
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Interleukin-2
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MAX protein, human
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Macromolecular Substances
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Myc associated factor X
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Proto-Oncogene Proteins c-myc
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Transcription Factors