Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation

AUTOR(ES)

Lin, Weei-Chin

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

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.

Documentos Relacionados

• Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage
• Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage
• ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
• The Telomeric Protein TRF2 Binds the ATM Kinase and Can Inhibit the ATM-Dependent DNA Damage Response
• Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage