RB Regulates the Stability and the Apoptotic Function of p53 via MDM2

Mol Cell. 1999 Feb;3(2):181-93. doi: 10.1016/s1097-2765(00)80309-3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • 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 / physiology
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-mdm2
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / deficiency
  • Retinoblastoma Protein / physiology*
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Macromolecular Substances
  • Nuclear Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2