The role of p53 as a transcription factor in the induction of apoptosis.
The tumor suppressor gene p53 plays a major role in the protection of cells from DNA damage. Activation of the protein in response to irradiation or genotoxic agents, and possibly by other signals, results in growth arrest at the G1 phase of the cell cycle or in apoptosis. While it has been shown that the ability of p53 to function as a sequence-specific transcriptional activator is necessary for the induction of growth arrest, the mechanism of p53-mediated apoptosis is not clear yet. In the present report we summarize the results obtained by several groups concerning p53-mediated apoptotic pathway. We suggest that p53 may induce apoptosis via a complex network of interacting pathways, which may be transcriptionally dependent or independent, depending on external signals and on the cellular context. Whatever the mechanisms are, the outcome-cell death by apoptosis-is a key function of the tumor suppressor p53.
Yonish-Rouach
E
E
Laboratoire de Cancérogenèse Moléculaire, UMR 217, DRR, SDV, CEA, Fontenay aux-Roses, France.
Choisy
C
C
Deguin
V
V
Breugnot
C
C
May
E
E
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D004249:DNA Damage; D006801:Humans; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D011994:Recombinant Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53