| First Author | Milton AH | Year | 2006 |
| Journal | EMBO J | Volume | 25 |
| Issue | 5 | Pages | 1046-57 |
| PubMed ID | 16482218 | Mgi Jnum | J:200296 |
| Mgi Id | MGI:5508255 | Doi | 10.1038/sj.emboj.7600999 |
| Citation | Milton AH, et al. (2006) 14-3-3 proteins integrate E2F activity with the DNA damage response. EMBO J 25(5):1046-57 |
| abstractText | 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. |
