| http://purl.uniprot.org/citations/21245099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21245099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21245099 | http://www.w3.org/2000/01/rdf-schema#comment | "The proapoptotic protein Noxa, a member of the BH3-only Bcl-2 protein family, can effectively induce apoptosis in cancer cells, although the relevant regulatory pathways have been obscure. Previous studies of the cytotoxic effects of α-tocopheryl succinate (α-TOS) on cancer cells identified a mechanism whereby α-TOS caused apoptosis requiring the Noxa-Bak axis. In the present study, ab initio analysis revealed a conserved FoxO-binding site (DBE; DAF-16 binding element) in the NOXA promoter, and specific affinity of FoxO proteins to this DBE was confirmed by fluorescence anisotropy. FoxO1 and FoxO3a proteins accumulated in the nucleus of α-TOS-treated cells, and the drug-induced specific FoxO1 association with the NOXA promoter and its activation were validated by chromatin immunoprecipitation. Using siRNA knockdown, a specific role for the FoxO1 protein in activating NOXA transcription in cancer cells was identified. Furthermore, the proapoptotic kinase Hippo/Mst1 was found to be strongly activated by α-TOS, and inhibiting Hippo/Mst1 by specific siRNA prevented phosphorylation of FoxO1 and its nuclear translocation, thereby reducing levels of NOXA transcription and apoptosis in cancer cells exposed to α-TOS. Thus, we have demonstrated that anticancer drugs, exemplified by α-TOS, induce apoptosis by a mechanism involving the Hippo/Mst1-FoxO1-Noxa pathway. We propose that activation of this pathway provides a new paradigm for developing targeted cancer treatments."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-10-2203"xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-10-2203"xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Boura E."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Boura E."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Obsil T."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Obsil T."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Dong L.F."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Dong L.F."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Neuzil J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Neuzil J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Ralph S.J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Ralph S.J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Chladova J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Chladova J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Prochazka L."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Prochazka L."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Rohlena J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Rohlena J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Truksa J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Truksa J."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Valis K."xsd:string |
| http://purl.uniprot.org/citations/21245099 | http://purl.uniprot.org/core/author | "Valis K."xsd:string |