Original Paper

Oncogene (2005) 24, 3726−3736. doi: 10.1038/sj.onc.1208491 Published online 14 March 2005
Published online 14 March 2005

BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase

Anis Feki1,2, Charles Edward Jefford1, Philip Berardi1,3, Jian-Yu Wu1, Laetitia Cartier1, Karl-Heinz Krause1 and Irmgard Irminger-Finger1

  1. 1Biology of Aging Laboratory, Department of Geriatrics, University of Geneva, Chemin de Petit Bel Air 2, CH-1225 Geneva/Chêne-Bourg, Switzerland
  2. 2Department of Gynecology and Obstetrics, University Hospital of Geneva, Geneva, Switzerland
  3. 3Biochemistry and Molecular Biology and Oncology, University of Calgary, Calgary, Canada

Correspondence: I Irminger-Finger, E-mail: [email protected]; URL: http://www.medecine.unige.ch/recherche/biologie_du_vieillissement/

Received 22 July 2004; Revised 08 November 2004; Accepted 20 December 2004; Published online 14 March 2005.



The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stability and apoptosis. The apoptotic activity of p53 is regulated by phosphorylation. We demonstrate that BARD1 binds to unphosphorylated and serine-15 phosphorylated forms of p53 in several cell types and that the region required for binding comprises the region sufficient for apoptosis induction. In addition, BARD1 binds to Ku-70, the regulatory subunit of DNA-PK, suggesting that the mechanism of p53-induced apoptosis requires BARD1 for the phosphorylation of p53. Upregulation of BARD1 alone is sufficient for stabilization of p53 and phosphorylation on serine-15, as shown in nonmalignant epithelial cells and ovarian cancer cells, NuTu-19, which are defective in apoptosis induction and express aberrant splice variants of BARD1. Stabilization and phosphorylation of p53 in NuTu-19 cells, as well as apoptosis, can be induced by the exogenous expression of wild-type BARD1, suggesting that BARD1, by binding to the kinase and its substrate, catalyses p53 phosphorylation.


apoptosis, BARD1, DNA-PK, Ku-70, p53, phosphorylation

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