A role for E2F1 in the induction of ARF, p53, and apoptosis during thymic negative selection

E2F transcriptional activity controls the expression of many of the genes r equired for G(1) to S phase progression. E2F1, one member of the E2F family , plays an important role in the induction of apoptosis. We have examined t he role of the E2F1 transcription factor in apoptosis during T-cell maturat ion in the thymus. We show that E2F1 is required for the apoptosis of autoi mmune immature T cells during thymic negative selection in vivo. This T-cel l receptor-mediated apoptosis coincides with the E2F1-dependent increase of p19-ARF mRNA and p53 protein levels. In contrast, E2F1 is not required for the induction of apoptosis by glucocorticoids or DNA damage. These results demonstrate a specific role for E2F1, which triggers a pathway leading to ARF and p53 induction, in a physiological apoptosis pathway that is uncoupl ed from a normal proliferative event.