Previous work has established a role for p53 in triggering apoptosis in response to DNA damage; p53 also induces apoptosis in response to deregulation of the Rb cell cycle pathway. The latter event is consistent with a role for the Rb-regulated E2F1 protein as a specific inducer of apoptosis and p53 accumulation. We now show that DNA damage leads to a specific induction of E2F1 accumulation, dependent on ATM kinase activity and that the specificity of E2F1 induction reflects a specificity in the phosphorylation of E2F1 by ATM as well as the related kinase ATR. We identify a site for ATM/ATR phosphorylation in the amino terminus of E2F1 and we show that this site is required for ATM-mediated stabilization of E2F1. Finally, we also show that E2F1 is required for DNA damaged induced apoptosis in mouse thymocytes. We conclude that the cellular response to DNA damage makes use of signals from the Rb/E2F cell cycle pathway.
SciCrunch® is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch® will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to SciCrunch®, however this is not currently a free service.