ABSTRACT 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

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. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS DECIPHERING UBE4B PHOSPHORYLATION DYNAMICS: A KEY MECHANISM IN P53 ACCUMULATION AND CANCER CELL RESPONSE TO DNA DAMAGE Article Open access 02 April

2025 P50 MONO-UBIQUITINATION AND INTERACTION WITH BARD1 REGULATES CELL CYCLE PROGRESSION AND MAINTAINS GENOME STABILITY Article Open access 06 October 2020 A P53–PHOSPHOINOSITIDE SIGNALOSOME

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871–875. Download references ACKNOWLEDGEMENTS We are grateful to MH Sow, A Caillon and C Genet for technical help. We are specifically indebted to Dr A Major for supply and sharing of

expertise in the NuTu-19 cell line. We are grateful to G Del Sal for his generous gift of expression plasmids of the p53 mutants and T McDonnell for PC3 cell line. This work was supported by

grant 3100-068222 from the Swiss National Science Foundation to IIF and KHK. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Biology of Aging Laboratory, Department of Geriatrics, University

of Geneva, Chemin de Petit Bel Air 2, CH-1225, Geneva/Chêne-Bourg, Switzerland Anis Feki, Charles Edward Jefford, Philip Berardi, Jian-Yu Wu, Laetitia Cartier, Karl-Heinz Krause & 

Irmgard Irminger-Finger * Department of Gynecology and Obstetrics, University Hospital of Geneva, Geneva, Switzerland Anis Feki * Biochemistry and Molecular Biology and Oncology, University

of Calgary, Calgary, Canada Philip Berardi Authors * Anis Feki View author publications You can also search for this author inPubMed Google Scholar * Charles Edward Jefford View author

publications You can also search for this author inPubMed Google Scholar * Philip Berardi View author publications You can also search for this author inPubMed Google Scholar * Jian-Yu Wu

View author publications You can also search for this author inPubMed Google Scholar * Laetitia Cartier View author publications You can also search for this author inPubMed Google Scholar *

Karl-Heinz Krause View author publications You can also search for this author inPubMed Google Scholar * Irmgard Irminger-Finger View author publications You can also search for this author

inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Feki, A., Jefford, C., Berardi, P. _et al._ BARD1 induces apoptosis by

catalysing phosphorylation of p53 by DNA-damage response kinase. _Oncogene_ 24, 3726–3736 (2005). https://doi.org/10.1038/sj.onc.1208491 Download citation * Received: 22 July 2004 * Revised:

08 November 2004 * Accepted: 20 December 2004 * Published: 14 March 2005 * Issue Date: 26 May 2005 * DOI: https://doi.org/10.1038/sj.onc.1208491 SHARE THIS ARTICLE Anyone you share the

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Nature SharedIt content-sharing initiative KEYWORDS * apoptosis * BARD1 * DNA-PK * Ku-70 * p53 * phosphorylation