RB regulates the stability and the apoptotic function of p53 via MDM2.
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.
Mesh Terms:
Apoptosis, Binding Sites, Carrier Proteins, Cell Cycle Proteins, DNA-Binding Proteins, E2F Transcription Factors, Female, Gene Expression, Genes, Retinoblastoma, Genes, p53, Humans, Macromolecular Substances, Nuclear Proteins, Peptide Fragments, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Transcription Factor DP1, Transcription Factors, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Apoptosis, Binding Sites, Carrier Proteins, Cell Cycle Proteins, DNA-Binding Proteins, E2F Transcription Factors, Female, Gene Expression, Genes, Retinoblastoma, Genes, p53, Humans, Macromolecular Substances, Nuclear Proteins, Peptide Fragments, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Transcription Factor DP1, Transcription Factors, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Mol. Cell
Date: Feb. 01, 1999
PubMed ID: 10078201
View in: Pubmed Google Scholar
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