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.

			Author Information
			(1) Department of Genetics, Howard Hughes
			Medical Institute, Durham, North Carolina
			27710, USA.

			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
			for MEDLINE]

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