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http://purl.uniprot.org/citations/31647098http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31647098http://www.w3.org/2000/01/rdf-schema#comment"Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5'-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkz1004"xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Chen Z."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Fang Y."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Cao J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Gao J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Lu J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Liang Y."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Luo J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Liu Z.P."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Wang M."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Zhao H."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Duan L."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Xiao G."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Rizo J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Chang C.M."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Zhang Q.J."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Lu J.'"xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Hsieh J.T."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Pong R.C."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Ahn J.M."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Hernandez E."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Roggero C.M."xsd:string
http://purl.uniprot.org/citations/31647098http://purl.uniprot.org/core/author"Dang A."xsd:string
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