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BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains

Oncogene volume 21, pages 6729–6739 (2002)Cite this article

Abstract

Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 is a 220-kDa protein that contains a tandem of two BRCA1 C-Terminal (BRCT) domains. Among missense and nonsense BRCA1 mutations responsible for family breast cancer, some are located into the BRCT tandem of BRCA1 coding sequence. In an attempt to understand how BRCT is critical for BRCA1 function, we search for partners of this BRCT tandem of BRCA1. Using a glutathione-S-transferase (GST) pull-down assay with murine cells, we isolated only one major BRCA1-interacting protein, further identified as Acetyl Coenzyme A (CoA) Carboxylase α (ACCA). We showed that this interaction is conserved through murine and human species. We also delineated the minimum interacting region as being the whole tandem of BRCT domains. We demonstrated that BRCA1 interacts in vitro and in vivo with ACCA. This interaction is completely abolished by five distinct germline BRCA1 deleterious mutations affecting the BRCT tandem of BRCA1. Interestingly, ACCA originally known as a rate-limiting enzyme for fatty acids biosynthesis, has been recently shown to be over-expressed in breast cancers and considered as a potential target for anti-neoplastic therapy. Furthermore, our observation is making a bridge between the genetic factors involved in susceptibility to breast and ovarian cancers, and environmental factors such as nutrition considered as key elements in the etiology of those cancers.

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Acknowledgements

We thank Jean Feunteun for the pCDNA3β-BRCA1wt. We would like to thank Marc Billaud and Jean-Pierre Rouault for advice and discussion. We are also very grateful to Marc Billaud and Robert Dante for critical reading of the manuscript. Clémence Magnard is the recipient of a fellowship from the Ligue Nationale contre le Cancer, Comité Départemental de la Haute-Savoie. The present work was supported by the Ligue Nationale contre le Cancer, Comité Départemental du Rhône and the CNRS (grant PCV97-102).

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  1. Richard Bachelier

    Present address: National Institute of Health, Building 10, 9N105, 9000 Rockville Pike, Bethesda, 20892, USA

  2. Gilbert M Lenoir

    Present address: Institut Gustave-Roussy, 39 Rue Camille-Desmoulins, Villejuif cedex, 94805, France

Authors and Affiliations

  1. Laboratoire de Génétique, CNRS UMR 5641, Université Claude Bernard Lyon I, Faculté de Médecine Rockefeller, 8 Avenue Rockefeller, Lyon, 69373, Cedex 08, France

    Clémence Magnard, Richard Bachelier, Anne Vincent, Gilbert M Lenoir & Nicole Dalla Venezia

  2. Laboratoire de Chimie des Protéines - DBMS, CEN - Grenoble, 17 Avenue des Martyrs, Grenoble cedex, 38054, France

    Michel Jaquinod & Sylvie Kieffer

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Correspondence to Nicole Dalla Venezia.

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Magnard, C., Bachelier, R., Vincent, A. et al. BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains. Oncogene 21, 6729–6739 (2002). https://doi.org/10.1038/sj.onc.1205915

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