| http://purl.uniprot.org/citations/33822745 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33822745 | http://www.w3.org/2000/01/rdf-schema#comment | "Endocrine resistance (EnR) in advanced prostate cancer is fatal. EnR can be mediated by androgen receptor (AR) splice variants, with AR splice variant 7 (AR-V7) arguably the most clinically important variant. In this study, we determined proteins key to generating AR-V7, validated our findings using clinical samples, and studied splicing regulatory mechanisms in prostate cancer models. Triangulation studies identified JMJD6 as a key regulator of AR-V7, as evidenced by its upregulation with in vitro EnR, its downregulation alongside AR-V7 by bromodomain inhibition, and its identification as a top hit of a targeted siRNA screen of spliceosome-related genes. JMJD6 protein levels increased (P < 0.001) with castration resistance and were associated with higher AR-V7 levels and shorter survival (P = 0.048). JMJD6 knockdown reduced prostate cancer cell growth, AR-V7 levels, and recruitment of U2AF65 to AR pre-mRNA. Mutagenesis studies suggested that JMJD6 activity is key to the generation of AR-V7, with the catalytic machinery residing within a druggable pocket. Taken together, these data highlight the relationship between JMJD6 and AR-V7 in advanced prostate cancer and support further evaluation of JMJD6 as a therapeutic target in this disease. SIGNIFICANCE: This study identifies JMJD6 as being critical for the generation of AR-V7 in prostate cancer, where it may serve as a tractable target for therapeutic intervention."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-20-1807"xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Kim S."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Ferreira A."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Yuan W."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Schofield C.J."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Islam M.S."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Uo T."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Kawamura A."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Pereira R."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Sharp A."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Tumber A."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Carreira S."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Al-Lazikani B."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Abboud M."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Alimonti A."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Miranda S."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Rodrigues D.N."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Crespo M."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Figueiredo I."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Welti J."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Plymate S.R."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Lambros M.B."xsd:string |
| http://purl.uniprot.org/citations/33822745 | http://purl.uniprot.org/core/author | "Christova R."xsd:string |