| http://purl.uniprot.org/citations/27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27494881 | http://www.w3.org/2000/01/rdf-schema#comment | "p66Shc attenuates mitogenic, prosurvival and chemotactic signaling and promotes apoptosis in lymphocytes. Consistently, p66Shc deficiency contributes to the survival and trafficking abnormalities of chronic lymphocytic leukemia (CLL) B cells. The mechanism of p66shc silencing in CLL B cells is methylation-independent, at variance with other cancer cell types. Here we identify STAT4 as a novel transcriptional regulator of p66Shc in B cells. Chromatin immunoprecipitation and reporter gene assays showed that STAT4 binds to and activates the p66shc promoter. Silencing or overexpression of STAT4 resulted in a co-modulation of p66Shc. IL-12-dependent STAT4 activation caused a coordinate increase in STAT4 and p66Shc expression, which correlated with enhanced B cell apoptosis. Treatment with the STAT4 inhibitor lisofylline reverted partly this effect, suggesting that STAT4 phosphorylation is not essential for but enhances p66shc transcription. Additionally, we demonstrate that CLL B lymphocytes have a STAT4 expression defect which partly accounts for their p66Shc deficiency, as supported by reconstitution experiments. Finally, we show that p66Shc participates in a positive feedback loop to promote STAT4 expression. These results provide new insights into the mechanism of p66Shc expression in B cells and its defect in CLL, identifying the STAT4/IL-12 pathway as a potential therapeutic target in this neoplasia."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.org/dc/terms/identifier | "doi:10.18632/oncotarget.10977"xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Semenzato G."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Trentin L."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Baldari C.T."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "D'Elios M.M."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Cattaneo F."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Capitani N."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Patrussi L."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/author | "Frezzato F."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/name | "Oncotarget"xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/pages | "57086-57098"xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/title | "Expression of the p66Shc protein adaptor is regulated by the activator of transcription STAT4 in normal and chronic lymphocytic leukemia B cells."xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/27494881 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27494881 |
| http://purl.uniprot.org/citations/27494881 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27494881 |
| http://purl.uniprot.org/uniprot/#_A0A510GAL5-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_A0A291B130-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_B7SIX5-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_B4DL02-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_B4DV04-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_B4DVP7-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |
| http://purl.uniprot.org/uniprot/#_B4DSY7-mappedCitation-27494881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27494881 |