| http://purl.uniprot.org/citations/21741956 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21741956 | http://www.w3.org/2000/01/rdf-schema#comment | "Emerging evidence suggests that Ret oncoproteins expressed in medullary thyroid cancer (MTC) might evade the pro-apoptotic function of the dependence receptor proto-Ret by directly impacting the apoptosis machinery. Identification of the molecular determinants of the interplay between Ret signaling and apoptosis might provide a relevant contribution to the optimization of Ret-targeted therapies. Here, we describe the cross-talk between Ret-M918T oncogenic mutant responsible for type 2B multiple endocrine syndrome (MEN2B), and components of death receptor-mediated extrinsic apoptosis pathway. In the human MEN2B-type MTC cell line MZ-CRC-1 expressing Ret-M918T, Ret was found associated with Fap-1, known as inhibitor of the CD95 death receptor trafficking to the cell membrane, and with procaspase-8, the initiator pro-form caspase in the extrinsic apoptosis pathway. Cell treatment with the anti-tumor Ret kinase inhibitor RPI-1 inhibited tyrosine phosphorylation of procaspase-8, likely inducing its local activation, followed by downregulation of both Ret and Fap-1, and translocation of CD95 into lipid rafts. According to the resulting increase of CD95 cell surface expression, the CD95 agonist antibody CH11 enhanced RPI-1-induced cell growth inhibition and apoptosis. RET RNA interference downregulated Fap-1 protein in MZ-CRC-1 cells, whereas exogenous RET-M918T upregulated Fap-1 in HEK293 cells. Overall, these data indicate that the Ret oncoprotein exerts opposing controls on Fap-1 and CD95, increasing Fap-1 expression and decreasing CD95 cell surface expression. The functional interplay of the Ret mutant with the extrinsic apoptosis pathway provides a mechanism possibly contributing to MTC malignant phenotype and a rational basis for novel therapeutic strategies combining Ret inhibitors and CD95 agonists."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bcp.2011.06.037"xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Cassinelli G."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Cuccuru G."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Bongarzone I."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Mondellini P."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Lanzi C."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Zunino F."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Zaffaroni N."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Casalini P."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Favini E."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Tortoreto M."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Nicolini V."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/author | "Petrangolini G."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/name | "Biochem Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/pages | "778-788"xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/title | "Interplay between Ret and Fap-1 regulates CD95-mediated apoptosis in medullary thyroid cancer cells."xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://purl.uniprot.org/core/volume | "82"xsd:string |
| http://purl.uniprot.org/citations/21741956 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21741956 |
| http://purl.uniprot.org/citations/21741956 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21741956 |
| http://purl.uniprot.org/uniprot/#_F5CNE9-mappedCitation-21741956 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21741956 |
| http://purl.uniprot.org/uniprot/#_B4DGX8-mappedCitation-21741956 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21741956 |
| http://purl.uniprot.org/uniprot/#_F8TLS5-mappedCitation-21741956 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21741956 |