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The E2F family is composed of at least eight E2F and two DP subunits, which in cells exist as E2F/DP heterodimers that bind to and regulate E2F target genes. While DP-1 is an essential and widespread component of E2F, much less is known about the DP-3 subunit, which exists as a number of distinct protein isoforms that differ in several respects including the presence of a nuclear localisation signal (NLS). We show here that the NLS region of DP-3 harbours a binding site for 14-3-3epsilon, and that binding of 14-3-3epsilon alters the cell cycle and apoptotic properties of E2F. DP-3 responds to DNA damage, and the interaction between DP-3 and 14-3-3epsilon is under DNA damage-responsive control. Further, 14-3-3epsilon is present in the promoter region of certain E2F target genes, and reducing 14-3-3epsilon levels induces apoptosis. These results identify a new level of control on E2F activity and, at a more general level, suggest that 14-3-3 proteins integrate E2F activity with the DNA damage response.

Original publication

DOI

10.1038/sj.emboj.7600999

Type

Journal article

Journal

EMBO J

Publication Date

08/03/2006

Volume

25

Pages

1046 - 1057

Keywords

14-3-3 Proteins, Amino Acid Sequence, Animals, Apoptosis, Apoptotic Protease-Activating Factor 1, COS Cells, Cell Cycle, Cercopithecus aethiops, DNA Damage, DNA-Binding Proteins, E2F1 Transcription Factor, E2F5 Transcription Factor, Genes, Tumor Suppressor, Humans, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Mutation, Nuclear Localization Signals, Nuclear Proteins, Promoter Regions, Genetic, Proteins, Sequence Homology, Amino Acid, Transcription Factors, Tumor Protein p73, Tumor Suppressor Proteins