| http://purl.uniprot.org/citations/17505062 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17505062 | http://www.w3.org/2000/01/rdf-schema#comment | "The breast cancer susceptibility gene BRCA1 is mutated in about one half of all hereditary breast cancer cases, and its expression is frequently decreased in sporadic cancers. Previously, we demonstrated a functional interaction between the BRCA1 and estrogen receptor-alpha (ER-alpha) proteins that causes inhibition of ER-alpha signaling. Here, we examined the role of growth factor signaling pathways in modulating this interaction. We found that underexpression of BRCA1 caused ligand-independent activation of ER-alpha that was mediated through phosphatidylinositol-3 kinase (PI3K)/c-Akt signaling. BRCA1 underexpression also enhanced estrogen-inducible ER-alpha activity in a PI3K/Akt-dependent manner. Exogenous c-Akt conferred estrogen-independent ER-alpha activation and rescued the BRCA1 repression of estrogen-stimulated ER-alpha activity. BRCA1 knockdown stimulated c-Akt activity, in part, by inhibiting the activity of protein phosphatase 2A, an enzyme that dephosphorylates Akt. ERs with point mutations of several growth factor-targeted serine residues (S167A, S118A, and S118/167A) were resistant to repression by BRCA1, although the single point mutant receptors still associated with the BRCA1 protein. The enhanced ER-alpha activity attributable to BRCA1 knockdown was dependent, in part, on serine residues 167 and 118 of ER-alpha. BRCA1 knockdown caused an increase in ER-alpha phosphorylation on serine-167 (but not serine-118 or serine-104/106) that was dependent on PI3K/Akt signaling and was mimicked by pharmacologic inhibition of protein phosphatase 2A. These findings suggest that BRCA1 regulates Akt signaling and the PI3K/Akt pathway modulates the ability of BRCA1 to repress ER-alpha, in part through serine phosphorylation events in the activation function-1 domain of ER-alpha."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.org/dc/terms/identifier | "doi:10.1210/me.2006-0397"xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/author | "Ma Y."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/author | "Hu C."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/author | "Fan S."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/author | "Riegel A.T."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/author | "Rosen E.M."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/pages | "1905-1923"xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/title | "Growth factor signaling pathways modulate BRCA1 repression of estrogen receptor-alpha activity."xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://purl.uniprot.org/core/volume | "21"xsd:string |
| http://purl.uniprot.org/citations/17505062 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17505062 |
| http://purl.uniprot.org/citations/17505062 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17505062 |
| http://purl.uniprot.org/uniprot/P38398#attribution-5A7C38A6F772F652EEB928C02B49B317 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/17505062 |
| http://purl.uniprot.org/uniprot/#_P03372-mappedCitation-17505062 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17505062 |
| http://purl.uniprot.org/uniprot/P03372 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/17505062 |