14-3-3 proteins integrate E2F activity with the DNA damage response
14-3-3 proteins integrate E2F activity with the DNA damage response
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DOI：
10.1038/sj.emboj.7600999
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发表时间：
2006-03-08
期刊：
影响因子：
11.4
通讯作者：
La Thangue, NB
中科院分区：
文献类型：
--
作者：
Milton, AH;Khaire, N;La Thangue, NB
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 14-3-3 epsilon, and that binding of 14-3-3 epsilon alters the cell cycle and apoptotic properties of E2F. DP-3 responds to DNA damage, and the interaction between DP-3 and 14-3-3 epsilon is under DNA damage-responsive control. Further, 14-3-3 epsilon is present in the promoter region of certain E2F target genes, and reducing 14-3-3 epsilon 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.
