Mechanisms of p53-mediated apoptosis

Cell Mol Life Sci. 1999 Jan;55(1):28-37. doi: 10.1007/s000180050267.

Abstract

The loss of p53-mediated apoptosis (programmed cell death) has been implicated as an important event in tumour progression in a number of systems. p53 can induce or potentiate apoptosis through several mechanisms, both by regulating the expression of genes which can participate in the apoptotic response and through transcriptionally independent means. There appears to be cell type variability in both the response to p53 expression and in the requirement for p53 transcriptional transactivation for the induction of apoptosis. It seems clear, however, that the induction of p53 in untransformed cells is more likely to result in cell-cycle arrest, whereas the expression of p53 in their transformed counterparts is more likely to result in the induction of apoptosis, and this may, in part, reflect the deregulated expression of E2F-1 in tumour cells. The synergistic action of p53 and E2F-1 in the induction of apoptosis has raised the possibility that the reactivation of p53 in transformed cells can be an effective tumour therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Apoptosis / genetics*
  • Carrier Proteins*
  • Caspases / genetics
  • Cell Cycle Proteins*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression Regulation / genetics
  • Mitochondria / metabolism
  • Models, Genetic
  • Receptors, Tumor Necrosis Factor / genetics
  • Repressor Proteins / genetics
  • Retinoblastoma-Binding Protein 1
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics
  • Tumor Suppressor Protein p53 / genetics*
  • fas Receptor

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Receptors, Tumor Necrosis Factor
  • Repressor Proteins
  • Retinoblastoma-Binding Protein 1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • fas Receptor
  • Caspases