Abstract
The binding of RB to MDM2 is shown to be essential for RB to overcome both the antiapoptotic function of MDM2 and the MDM2-dependent degradation of p53. The RB-MDM2 interaction does not prevent MDM2 from inhibiting p53-dependent transcription, but the RB-MDM2 complex still binds to p53. Since RB specifically rescues the apoptotic function but not the transcriptional activity of p53 from negative regulation by MDM2, transactivation by wild-type p53 is not required for the apoptotic function of p53. However, an RB-MDM2-p53 trimeric complex is active in p53-mediated transrepression. These data link directly the function of two tumor suppressor proteins and demonstrate a novel role of RB in regulating the apoptotic function of p53.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology*
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Binding Sites
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Carrier Proteins*
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Cell Cycle Proteins*
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DNA-Binding Proteins*
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E2F Transcription Factors
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Female
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Gene Expression
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Genes, Retinoblastoma
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Genes, p53
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Humans
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Macromolecular Substances
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Nuclear Proteins*
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Peptide Fragments / physiology
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Phosphorylation
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Protein Binding
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Protein Processing, Post-Translational
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-mdm2
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Retinoblastoma Protein / chemistry
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Retinoblastoma Protein / deficiency
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Retinoblastoma Protein / physiology*
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors / metabolism
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / physiology*
Substances
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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E2F Transcription Factors
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Macromolecular Substances
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Nuclear Proteins
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Peptide Fragments
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2