Abstract
p53 is known to repress transcription of a number of genes, but the mechanism of p53 recruitment to these target genes is unknown. The c-myb proto-oncogene product (c-Myb) positively regulates proliferation of immature hematopoietic cells, whereas p53 blocks cell cycle progression. Here, we demonstrate that p53 inhibits c-Myb-induced transcription and transformation by directly binding to c-Myb. The ability of c-Myb to maintain the undifferentiated state of M1 cells was also suppressed by p53. p53 did not affect the ability of c-Myb to bind to DNA but formed a ternary complex with the corepressor mSin3A and c-Myb. Thus, p53 antagonizes c-Myb by recruiting mSin3A to down-regulate specific Myb target genes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Cell Line
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Cell Proliferation
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DNA / chemistry
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DNA / metabolism
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Down-Regulation
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Electrophoresis, Polyacrylamide Gel
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Gene Expression Regulation
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Glutathione Transferase / metabolism
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Hematopoietic Stem Cells / metabolism
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Humans
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Immunoprecipitation
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Interleukin-6 / metabolism
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Luciferases / metabolism
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Models, Biological
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Oligonucleotide Array Sequence Analysis
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myb / metabolism
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Proto-Oncogene Proteins c-myb / physiology*
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RNA / chemistry
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Repressor Proteins / metabolism*
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Sin3 Histone Deacetylase and Corepressor Complex
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Transcription, Genetic
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Transcriptional Activation*
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Transfection
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Tumor Suppressor Protein p53 / metabolism*
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Up-Regulation
Substances
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Interleukin-6
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MAS1 protein, human
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myb
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Repressor Proteins
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SIN3A transcription factor
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Tumor Suppressor Protein p53
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RNA
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DNA
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Luciferases
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Glutathione Transferase
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Sin3 Histone Deacetylase and Corepressor Complex