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| Subject Categories: Chromatin & Transcription | Cell Cycle |
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| The EMBO Journal
(2006) 25, 1046–1057, doi:10.1038/sj.emboj.7600999 Published online 16 February 2006 |
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| 14-3-3 proteins integrate E2F activity with the DNA damage response |
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| Alasdair H Milton, Nandkumar Khaire, Laura Ingram, Amanda J O'donnell and Nicholas B La Thangue |
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Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, UK To whom correspondence should be addressed Nicholas B La Thangue, Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, Oxford OX3 9DU, UK. Tel.: +44 1865 220342; Fax: +44 1865 222754; E-mail: nick.lathangue@ndcls.ox.ac.uk Received 21 February 2005; Accepted 19 January 2006; Published online 16 February 2006. |
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| Abstract |
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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 14-3-3 , and that binding of 14-3-3 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 is under DNA damage-responsive control. Further, 14-3-3 is present in the promoter region of certain E2F target genes, and reducing 14-3-3 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. |
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| Keywords: cancer, cell cycle, E2F, transcription, 14-3-3 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article (04 Jan 1999) A functionally distinct member of the DP family of E2F subunits Oncogene Scientific Correspondence A functionally distinct member of the DP family of E2F subunits Oncogene Scientific Correspondence Chk2 activates E2F-1 in response to DNA damage Nature Cell Biology Article (01 May 2003) |
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