{"doi":"10.1101/2021.06.03.446940","title":"AR-V7 exhibits non-canonical mechanisms of nuclear import and chromatin engagement in Castrate-Resistant Prostate Cancer","abstract":"Summary Expression of the AR splice variant, AR-V7, in prostate cancer is correlated with poor patient survival and resistance to AR targeted therapies and taxanes. Currently, there is no specific inhibitor of AR-V7, while the molecular mechanisms regulating its biological function are not well elucidated. Here we report that AR-V7 has unique biological features that functionally differentiate it from canonical AR-fl or from the second most prevalent variant, AR-v567. First, AR-V7 exhibits fast nuclear import kinetics via a pathway distinct from the nuclear localization signal dependent importin-α /β pathway used by AR-fl and AR-v567. We also show that the dimerization box domain, known to mediate AR dimerization and transactivation, is required for AR-V7 nuclear import but not for AR-fl. Once in the nucleus, AR-V7 is transcriptionally active, yet exhibits unusually high intranuclear mobility and transient chromatin interactions, unlike the stable chromatin association of liganded AR-fl. The high intranuclear mobility of AR-V7 together with its high transcriptional output, suggest a Hit-and-Run mode of transcription. Our findings reveal unique mechanisms regulating AR-V7 activity, offering the opportunity to develop selective therapeutic interventions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218831,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":817441,"name":"Mohd Azrin Bin Jamalruddin","orcid":null,"position":1,"is_corresponding":false},{"id":816955,"name":"CheukMan C. Au","orcid":"0000-0001-8289-7365","position":2,"is_corresponding":false},{"id":516873,"name":"Eiman Mukhtar","orcid":null,"position":3,"is_corresponding":false},{"id":816956,"name":"Luigi Portella","orcid":"0000-0002-8679-3309","position":4,"is_corresponding":false},{"id":816957,"name":"Adeline Berger","orcid":"0000-0003-2986-4489","position":5,"is_corresponding":false},{"id":516087,"name":"Daniel Worroll","orcid":"0000-0001-7351-676X","position":6,"is_corresponding":false},{"id":649400,"name":"David S. Rickman","orcid":"0000-0001-7420-5883","position":7,"is_corresponding":false},{"id":354017,"name":"David M. Nanus","orcid":"0000-0003-3514-2976","position":8,"is_corresponding":false},{"id":333546,"name":"Paraskevi Giannakakou","orcid":"0000-0001-7378-262X","position":9,"is_corresponding":false},{"id":817440,"name":"Seaho Kim","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:53:33.915158Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}