ACCA phosphopeptide recognition by the BRCT repeats of BRCA1
| Autor: | Karen Moreau, Nicole Dalla Venezia, Hind Ray, Isabelle Callebaut, Eva Dizin |
|---|---|
| Přispěvatelé: | Génétique moléculaire, signalisation et cancer (GMSC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Repetitive Sequences Amino Acid phosphopeptide endocrine system diseases Immunoprecipitation Sequence analysis Protein Conformation Biology Protein–protein interaction 03 medical and health sciences protein modelling 0302 clinical medicine Protein structure Structural Biology Serine Humans Phosphorylation skin and connective tissue diseases Molecular Biology Cells Cultured 030304 developmental biology Genetics 0303 health sciences Acca Phosphopeptide BRCA1 Protein biology.organism_classification Phosphoproteins protein–protein interaction 030220 oncology & carcinogenesis ACCA BRCT Function (biology) Acetyl-CoA Carboxylase |
| Zdroj: | Journal of Molecular Biology Journal of Molecular Biology, Elsevier, 2006, 359, pp.973-982. ⟨10.1016/j.jmb.2006.04.010⟩ Journal of Molecular Biology, 2006, 359, pp.973-982. ⟨10.1016/j.jmb.2006.04.010⟩ |
| ISSN: | 0022-2836 1089-8638 |
| DOI: | 10.1016/j.jmb.2006.04.010⟩ |
| Popis: | Article in Press, Corrected Proof; The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263. |
| Databáze: | OpenAIRE |
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