Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO J. 1996 Jul 15;15(14):3693-701.

Transcriptional activation by p53, but not induction of the p21 gene, is essential for oncogene-mediated apoptosis.

Author information

  • 1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.

Abstract

The p53 tumor suppressor limits cellular proliferation by inducing either G1 arrest or apoptosis, depending on the cellular context. To determine if these pathways are mechanistically distinct, we have examined the effects of different p53 mutants in p53 null primary mouse embryo fibroblasts. We chose this system as it is highly physiological and ensures that the interpretation of the results will not be confounded by the presence of endogenous p53 or oncoproteins which target p53. Using single cell microinjection assays for both G1 arrest and apoptosis, with loss-of-function and chimeric gain-of-function mutants, we have demonstrated that transcriptional activation is critical for both processes. Replacement of the p53 activation domain with that of VP16, or replacement of the p53 oligomerization domain with that of GCN4, reconstituted both G1 arrest and apoptosis activities. However, despite the importance of transcriptional activation in both processes, the target gene requirements are different. The p21 cyclin-dependent kinase inhibitor, which has been shown to be a direct target of p53 and a component of the radiation-induced G1 arrest response, is dispensable for oncogene-induced apoptosis, suggesting that these two p53-dependent transcriptional pathways are distinct.

PMID:
8758936
[PubMed - indexed for MEDLINE]
PMCID:
PMC452024
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk