{"doi":"10.17615/dnjj-4962","title":"pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2","abstract":"The VHL tumor suppressor protein (pVHL) is part of an E3 ubiquitin ligase that targets HIF for destruction. pVHL-defective renal carcinoma cells exhibit increased NF-κB activity but the mechanism is unclear. NF-κB affects tumorigenesis and therapeutic resistance in some settings. We found that pVHL associates with the NF-κB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C-terminus by CK2. Elimination of these sites markedly enhanced Card9's ability to activate NF-κB in VHL+/+ cells and Card9 siRNA normalized NF-κB activity in VHL−/− cells and restored their sensitivity to cytokine-induced apoptosis. Furthermore, downregulation of Card9 in VHL−/− cancer cells reduced their tumorigenic potential. Therefore pVHL can serve as an adaptor for both an ubiquitin conjugating enzyme and for a kinase. The latter activity, which promotes Card9 phosphorylation, links pVHL to control of NF-κB activity and tumorigenesis.","journal":"UNC Libraries","year":2020,"id":144625,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":613745,"name":"Liang Zhang","orcid":"0000-0003-4396-9199","position":1,"is_corresponding":false},{"id":407735,"name":"William Y. Kim","orcid":"0000-0001-7922-2156","position":2,"is_corresponding":false},{"id":16672,"name":"Benjamin L. Ebert","orcid":"0000-0003-0197-5451","position":3,"is_corresponding":false},{"id":613746,"name":"Yan Qin","orcid":"0000-0002-6187-601X","position":4,"is_corresponding":false},{"id":425957,"name":"Aria F. Olumi","orcid":"0000-0001-5356-2558","position":5,"is_corresponding":false},{"id":613747,"name":"Susanne Schlisio","orcid":"0000-0002-2605-3771","position":6,"is_corresponding":false},{"id":63522,"name":"William G. Kaelin","orcid":"0000-0002-0574-4856","position":7,"is_corresponding":false},{"id":613748,"name":"Xiao–Ping Zhang","orcid":"0000-0001-5241-0069","position":8,"is_corresponding":false},{"id":613749,"name":"Yang Haifeng","orcid":"0000-0002-3340-1455","position":9,"is_corresponding":false},{"id":613744,"name":"Yoji Andrew Minamishima","orcid":"0000-0001-7995-9318","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:48.191325Z","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":[]}