{"doi":"10.17615/tw5m-ha65","title":"Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication","abstract":"The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression.","journal":"UNC Libraries","year":2020,"id":136143,"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":0.9558,"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":594144,"name":"Natalia Reszka-Blanco","orcid":null,"position":1,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":2,"is_corresponding":false},{"id":594556,"name":"Christopher M. Murphy","orcid":"0000-0003-2552-7514","position":3,"is_corresponding":false},{"id":432476,"name":"Yanping Xu","orcid":"0000-0003-2750-5466","position":4,"is_corresponding":false},{"id":435873,"name":"Feng Li","orcid":"0000-0003-3169-6349","position":5,"is_corresponding":false},{"id":355605,"name":"Xiaodong Li","orcid":"0000-0002-2089-5046","position":6,"is_corresponding":false},{"id":522941,"name":"Yaxu Wu","orcid":null,"position":7,"is_corresponding":false},{"id":11782,"name":"Yanbao Yu","orcid":"0000-0003-2994-1974","position":8,"is_corresponding":false},{"id":63630,"name":"Yue Xiong","orcid":"0000-0003-2744-6566","position":9,"is_corresponding":false},{"id":594555,"name":"Kouki Nio","orcid":"0000-0002-0971-8313","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:48.793683Z","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":[]}