p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes.

Abstract:

:The tumour suppressor p53 is required to induce programmed cell death (apoptosis) by DNA-damaging agents. As p53 is a transcriptional activator that mediates gene induction after DNA damage, it has been proposed to be a genetic switch that activates apoptosis-mediator genes. Here we evaluate the role of p53 in DNA-damage-induced apoptosis by establishing derivatives of GHFT1 cells, that are somatotropic progenitors immortalized by expression of SV40 T-antigen, which express a temperature-sensitive p53 mutant. In these cells induction of apoptosis by DNA damage depends strictly on p53 function. A shift to the permissive temperature triggers apoptosis following DNA damage, but this is independent of new RNA or protein synthesis. The extent of apoptotic DNA cleavage is directly proportional to the period during which p53 is functional. These results do not support the proposal that p53 is an activator of apoptosis-mediator genes but rather indicate that p53 either represses genes necessary for cell survival or is a component of the enzymatic machinery for apoptotic cleavage or repair of DNA.

journal_name

Nature

journal_title

Nature

authors

Caelles C,Helmberg A,Karin M

doi

10.1038/370220a0

subject

Has Abstract

pub_date

1994-07-21 00:00:00

pages

220-3

issue

6486

eissn

0028-0836

issn

1476-4687

journal_volume

370

pub_type

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