PubMed Journals: Genes Dev
Source: PMID: 11459832
⇦ ⇨ Genes Dev. 2001 Jul 15;15(14):1833-44.
Selective induction of E2F1 in response
to DNA damage, mediated by ATM-dependent phosphorylation.
Lin WC(1), Lin FT, Nevins JR.
(1) Department of Genetics, Howard Hughes
Medical Institute, Durham, North Carolina
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.
PMCID: PMC312742 PMID: 11459832 [Indexed