Apoptosis-stimulating protein of p53-2 (ASPP2/^53BP2L) is an E2F target gene

The p53 pathway is a central apoptotic regulator. Deregulation of the Rb/E2F pathway occurs in a majority of tumors, resulting in both unrestrained proliferation and enhanced apoptosis sensitivity via p53-dependent and independent mechanisms. However, the mechanisms coupling the p53 and Rb/E2F pathways remain incompletely understood. We report that ASPP2/^53BP2L, a p53/p73-binding protein that promotes p53/p73-dependent apoptosis, is an E2F target gene. The ASPP2/^53BP2L promoter was identified and ectopic expression of transcription-competent E2F-1 (E2F-2 and E2F-3) stimulated an ASPP2/^53BP2L promoter-luciferase reporter. Mutational analysis of the ASPP2/^53BP2L promoter identified E2F-binding sites that cooperate for E2F-1 induction and basal repression of ASPP2/^53BP2L. Moreover, endogenous ASPP2/^53BP2L levels increased after E2F-1 expression, and E2F-1 bound the endogenous ASPP2/^53BP2L promoter after chromatin immunoprecipitation. Typical for an E2F target, ASPP2/^53BP2L expression was maximal in early S-phase. Thus, ASPP2/^53BP2L is downstream of E2F, suggesting that it functions as a common link between the p53/p73 and Rb/E2F apoptotic pathways.