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http://purl.uniprot.org/citations/21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21743495http://www.w3.org/2000/01/rdf-schema#comment"The ubiquitously expressed 14-3-3 proteins regulate many pathways involved in transformation. Previously, we found that 14-3-3ζ overexpression increased Akt phosphorylation in human mammary epithelial cells. Here, we investigated the clinical relevance and molecular mechanism of 14-3-3ζ-overexpression-mediated Akt phosphorylation, and its potential impact on breast cancer progression. We found that 14-3-3ζ overexpression was significantly (P=0.005) associated with increased Akt phosphorylation in human breast tumors. Additionally, 14-3-3ζ overexpression combined with strong Akt phosphorylation was significantly (P=0.01) associated with increased cancer recurrence in patients. In contrast, knockdown of 14-3-3ζ expression by small interfering RNA in cancer cell lines and tumor xenografts reduced Akt phosphorylation. Furthermore, 14-3-3ζ enhanced Akt phosphorylation through activation of phosphoinositide 3-kinase (PI3K). Mechanistically, 14-3-3ζ bound to the p85 regulatory subunit of PI3K and increased PI3K translocation to the cell membrane. A single 14-3-3-binding motif encompassing serine 83 on p85 is largely responsible for 14-3-3ζ-mediated p85 binding and PI3K/Akt activation. Mutation of serine 83 to alanine on p85 inhibited 14-3-3ζ binding to the p85 subunit of PI3K, reduced PI3K membrane localization and activation, impeded anchorage-independent growth and enhanced stress-induced apoptosis. These findings revealed a novel mechanism by which 14-3-3ζ overexpression activates PI3K, a key node in the mitogenic signaling network known to promote malignancies in many cell types."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.org/dc/terms/identifier"doi:10.1038/onc.2011.284"xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Li P."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Mori S."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Yang J."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Zhou X."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Xu J."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Yu D."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Neal C.L."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Wyszomierski S.L."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/author"Neal N.N."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/name"Oncogene"xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/pages"897-906"xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/title"Overexpression of 14-3-3zeta in cancer cells activates PI3K via binding the p85 regulatory subunit."xsd:string
http://purl.uniprot.org/citations/21743495http://purl.uniprot.org/core/volume"31"xsd:string
http://purl.uniprot.org/citations/21743495http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21743495
http://purl.uniprot.org/citations/21743495http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21743495
http://purl.uniprot.org/uniprot/#_D0PNI1-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495
http://purl.uniprot.org/uniprot/#_A0A2X0SFG1-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495
http://purl.uniprot.org/uniprot/#_B7Z2E6-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495
http://purl.uniprot.org/uniprot/#_B0AZS6-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495
http://purl.uniprot.org/uniprot/#_B3KWZ7-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495
http://purl.uniprot.org/uniprot/#_B7Z2N8-mappedCitation-21743495http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21743495