Abstract
Myc proteins are basic helix-loop-helix/leucine-zipper proteins that bind to specific DNA sequences. In vivo, Myc proteins have been found associated with Max, another basic helix-loop-helix/leucine-zipper protein. However, it is not known to what extent the dimerization of Myc with Max is required for the manifestation of the Myc-induced phenotype. To investigate this, we constructed a dominant-negative mutant of Max, named dMax, that inhibits sequence-specific DNA binding of Myc proteins. Using a rat neuroblastoma model system, we show that dMax reverts N-Myc-induced changes in cellular gene expression. A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression. These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo.
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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Base Sequence
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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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Cloning, Molecular
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Genes, Dominant
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Genes, myc*
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Molecular Sequence Data
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Mutagenesis
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Neuroblastoma
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Oligodeoxyribonucleotides
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Polymerase Chain Reaction / methods
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Protein Biosynthesis
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Rats
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Sequence Deletion
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Transcription Factors*
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
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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Max protein, rat
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Myc associated factor X
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Oligodeoxyribonucleotides
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Proto-Oncogene Proteins c-myc
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Transcription Factors