| http://purl.uniprot.org/citations/26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26891695 | http://www.w3.org/2000/01/rdf-schema#comment | "A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signaling by activating the MEK-ERK pathway. Low kinase activity of A-Raf toward MEK suggested that A-Raf might have alternative functions. We recently identified A-Raf as a potent inhibitor of the proapoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities including head and neck, colon, and breast. Independent of kinase activity, A-Raf binds to MST2 thereby efficiently inhibiting apoptosis. Here, we show that the interaction of A-Raf with the MST2 pathway is regulated by subcellular compartmentalization. Although in proliferating normal cells and tumor cells A-Raf localizes to the mitochondria, differentiated non-carcinogenic cells of head and neck epithelia, which express A-Raf at the plasma membrane. The constitutive or induced re-localization of A-Raf to the plasma membrane compromises its ability to efficiently sequester and inactivate MST2, thus rendering cells susceptible to apoptosis. Physiologically, A-Raf re-localizes to the plasma membrane upon epithelial differentiation in vivo. This re-distribution is regulated by the scaffold protein kinase suppressor of Ras 2 (KSR2). Downregulation of KSR2 during mammary epithelial cell differentiation or siRNA-mediated knockdown re-localizes A-Raf to the plasma membrane causing the release of MST2. By using the MCF7 cell differentiation system, we could demonstrate that overexpression of A-Raf in MCF7 cells, which induces differentiation. Our findings offer a new paradigm to understand how differential localization of Raf complexes affects diverse signaling functions in normal cells and carcinomas."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.org/dc/terms/identifier | "doi:10.1038/cdd.2016.2"xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Gires O."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Kolch W."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Blanco A."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Mack B."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Rauch J."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Volinsky N."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "Vandamme D."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/author | "McCann B."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/name | "Cell Death Differ"xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/pages | "1283-1295"xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/title | "Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation."xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://purl.uniprot.org/core/volume | "23"xsd:string |
| http://purl.uniprot.org/citations/26891695 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26891695 |
| http://purl.uniprot.org/citations/26891695 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26891695 |
| http://purl.uniprot.org/uniprot/#_A0A024R178-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_P10398-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3F2-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_B4DMG5-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_B4DV85-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_Q59HC8-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |
| http://purl.uniprot.org/uniprot/#_Q96II5-mappedCitation-26891695 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26891695 |