A two-step mechanism for cell fate decision by coordination of nuclear and mitochondrial p53 activities.

ABSTRACT: The tumor suppressor p53 has a crucial role in the DNA damage response. Here, we proposed an integrated model of the p53 network and explored how the nuclear and mitochondrial p53 pathways are coordinated to determine cell fates after [Formula: see text]-irradiation in radiosensitive tissues. Using numerical simulations, we found that depending on the extent of DNA damage, cells may survive, commit apoptosis after cell cycle arrest, or undergo apoptosis soon after irradiation. There exists a large cell-to-cell variability in outcome because of stochasticity in the generation and repair of DNA damage as well as cellular heterogeneity. At the cell population level, there occur two waves of apoptosis: a fast wave mediated by mitochondrial p53 within three hours postirradiation, and a slow wav

SUBMITTER: Tian XJ 

PROVIDER: S-EPMC3367989 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature