BRCA1 interacts with poly(A)-binding protein: implication of BRCA1 in translation regulation.
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.
Dizin
Eva
E
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.
Gressier
Céline
C
Magnard
Clémence
C
Ray
Hind
H
Décimo
Didier
D
Ohlmann
Théophile
T
Dalla Venezia
Nicole
N
D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D009154:Mutation; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; D039122:Poly(A)-Binding Protein I; D025521:Tumor Suppressor Proteins