Coordination between cell cycle progression and cell fate decision by the p53 and E2F1 pathways in response to DNA damage.

ABSTRACT: After DNA damage, cells must decide between different fates including growth arrest, DNA repair, and apoptosis. Both p53 and E2F1 are transcription factors involved in the decision process. However, the mechanism for cross-talk between the p53 and E2F1 pathways still remains unclear. Here, we proposed a four-module kinetic model of the decision process and explored the interplay between these two pathways in response to ionizing radiation via computer simulation. In our model the levels of p53 and E2F1 separately exhibit pulsatile and switching behaviors. Upon DNA damage, p53 is first activated, whereas E2F1 is inactivated, leading to cell cycle arrest in the G(1) phase. We found that the ultimate decision between cell life and death is determined by the number of p53 pulses depending on t

SUBMITTER: Zhang XP 

PROVIDER: S-EPMC2951231 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature