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14‐3‐3 proteins integrate E2F activity with the DNA damage response
Author(s) -
Milton Alasdair H,
Khaire Nandkumar,
Ingram Laura,
O'donnell Amanda J,
La Thangue Nicholas B
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600999
Subject(s) - biology , classics , library science , history , computer science
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 14‐3‐3ε, and that binding of 14‐3‐3ε alters the cell cycle and apoptotic properties of E2F. DP‐3 responds to DNA damage, and the interaction between DP‐3 and 14‐3‐3ε is under DNA damage‐responsive control. Further, 14‐3‐3ε is present in the promoter region of certain E2F target genes, and reducing 14‐3‐3ε 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.