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Article

  • The EMBO Journal (2005) 24, 2768 - 2782
  • doi:10.1038/sj.emboj.7600735

Published online: 21 July 2005

Cell cycle-dependent nuclear retention of p53 by E2F1 requires phosphorylation of p53 at Ser315

Valentina Fogal1, Jung-Kuang Hsieh1, Christophe Royer1, Shan Zhong1 and Xin Lu1

  1. Ludwig Institute for Cancer Research, University College London Branch, London, UK

Correspondence to:

Xin Lu, Ludwig Institute for Cancer Research, University College London Branch, 91 Riding House Street, London W1W 7BS, UK. Tel.: +44 207 878 4112; Fax: +44 207 878 4141; E-mail: x.lu@ludwig.ucl.ac.uk

Received 15 June 2004; Accepted 8 June 2005

We show here that the cell cycle-dependent DNA-binding and transcriptional activity of p53 correlates with E2F expression in human primary fibroblasts. E2F1 binds and stimulates DNA-binding, transactivation and apoptotic functions of p53 but not p63 and p73. E2F1 binds residues 347–370 of p53 and enhances nuclear retention of Ser315 phosphorylated p53. This regulation of p53 by E2F1 is cell cycle dependent, as the cellular distribution of Ser315 phosphorylated p53 is associated with the periodic expression of E2F and cyclin A throughout the cell cycle. This is the first demonstration that the activities of p53 are regulated during the cell cycle by E2F/p53 interactions and that phosphorylation of p53 at Ser315 is required for this regulation.

  • Keywords:

    • cell cycle,
    • E2F1,
    • nuclear export,
    • p53,
    • Ser315