HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 34, 24236-24246, August 25, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/34/24236    most recent M602176200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dizin, E. Articles by Venezia, N. D. Search for Related Content PubMed PubMed Citation Articles by Dizin, E. Articles by Venezia, N. D. Social Bookmarking                      What's this?

BRCA1 Interacts with Poly(A)-binding Protein

IMPLICATION OF BRCA1 IN TRANSLATION REGULATION^*

Eva Dizin¹, Céline Gressier, Clémence Magnard², Hind Ray³, Didier Décimo, Théophile Ohlmann, and Nicole Dalla Venezia⁴

From the CNRS UMR 5201, Laboratoire de Génétique Moléculaire, Signalisation et Cancer, Université Claude Bernard Lyon I, Facultéde Médecine Rockefeller, 8 Avenue Rockefeller, 69373 Lyon cedex 08, France and INSERM, U 412, Ecole Normale Supérieure de Lyon, LaboRetro, Unité de Virologie Humaine, IFR 128, 46 Allée d'Italie, 69364 Lyon 07, France

BRCA1 has been implicated in a number of cellular processes, including transcription regulation, DNA damage repair, cell cycle control, and apoptosis. We identified poly(A)-binding protein 1 (PABP) as a novel BRCA1-interacting protein in a yeast two-hybrid screen and confirmed the interaction by in vitro assays and coimmunoprecipitation in mammalian cells. Endogenous interaction between BRCA1 and PABP was also observed. This interaction was abolished by BRCA1 cancer-associated mutations, suggesting that it may be physiologically relevant. Deletion mapping demonstrated that the RNA recognition motifs 1–4 region of PABP is required to mediate the interaction with BRCA1. To understand the biological function of the BRCA1-PABP complex, we sought to determine whether BRCA1 is a modulator of translation. We showed here that inhibition of endogenous BRCA1 using a small interfering RNA-based approach decreased protein synthesis. Conversely, overexpression of BRCA1 activated translation. Using a RNA transfection approach, we clearly showed that BRCA1 modulates translation, independently of any transcriptional activity. The data presented here suggest that BRCA1 modulates protein synthesis via its interaction with PABP, providing a novel mechanism by which BRCA1 may exert its tumor suppressor function.

Received for publication, March 7, 2006 , and in revised form, June 8, 2006.

^* The present work was supported by the Ligue Nationale Contre le Cancer, Comité Départemental du Rhône and Comité Départemental de la Haute-Savoie, and the Association pour la Recherche sur le Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of a fellowship from the French Ministry of Research.

² Current address: Yole Developpment, 45 Rue Sainte Geneviève, 69006 Lyon, France.

³ Recipient of a fellowship from the Association pour la Recherche sur le Cancer.

⁴ To whom correspondence should be addressed. Tel.: 33-478-777-213; Fax: 33-478-777-220; E-mail: dalla{at}rockefeller.univ-lyon1.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. S. Rifo, E. P. Ricci, D. Decimo, O. Moncorge, and T. Ohlmann Back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(A) synergy and the selective advantage of IRES-driven translation Nucleic Acids Res., September 25, 2007; 35(18): e121 - e121. [Abstract] [Full Text] [PDF]