{"doi":"10.1128/jvi.01298-20","title":"Ubiquitin Modification of the Epstein-Barr Virus Immediate Early Transactivator Zta","abstract":"<jats:p>Epstein-Barr virus (EBV) is a ubiquitous human pathogen and associated with various human diseases. EBV undergoes latency and lytic replication stages in its life cycle. The transition into the lytic replication stage, at which virus is produced, is mainly regulated by the viral gene product, Zta. Therefore, the regulation of Zta function becomes a central issue regarding viral biology and pathogenesis. Known modifications of Zta include phosphorylation and sumoylation. Here, we report the role of ubiquitination in regulating Zta function. We found that Zta is subjected to ubiquitination in both EBV-infected and EBV-negative cells. The ubiquitin modification targets 4 lysine residues on Zta, leading to both mono- and polyubiquitination of Zta. Ubiquitination of Zta affects the protein’s stability and likely contributes to the progression of viral lytic replication. The function and fate of Zta may be determined by the specific lysine residue being modified.</jats:p>","journal":"Journal of Virology","year":2020,"id":20703,"datarank":0.6838164760574,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.24215062918243388,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.24215062918243388,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":135942,"name":"Asuka Nanbo","orcid":null,"position":1,"is_corresponding":false},{"id":135943,"name":"David Becnel","orcid":null,"position":2,"is_corresponding":false},{"id":135944,"name":"Zhiqiang Qin","orcid":"0000-0002-1130-4689","position":3,"is_corresponding":false},{"id":135945,"name":"Gilbert F. Morris","orcid":null,"position":4,"is_corresponding":false},{"id":2699,"name":"Li Li","orcid":"0000-0001-6746-4297","position":5,"is_corresponding":false},{"id":135946,"name":"Zhen Lin","orcid":"0000-0002-9229-053X","position":6,"is_corresponding":false},{"id":135941,"name":"Mengmeng Zhao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32847852","pmcid":"PMC7592219","openalex_id":"https://openalex.org/W3080799775","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"P20 GM121288","title":null},{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"JP17K4567","title":null},{"funder_name":"Tulane University","grant_id":"Faculty research pilot grant","title":null},{"funder_name":"Tulane University","grant_id":"Carol Lavin Bernick faculty grant","title":null},{"funder_name":"CRDF Global","grant_id":"U.S.-Japan Cooperative Medical Sciences Program Collaborative Award","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"U54 GM104940","title":null},{"funder_name":"National Institutes of Health","grant_id":"1P20GM121288-01","title":"Center for Translational Viral Oncology (CTVO)"},{"funder_name":"Takeda Science Foundation","grant_id":"","title":null}],"total_grants":8,"fwci":0.7669,"citation_percentile":0.73962722,"influential_citations":1,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":6},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"green","license":"ASM Journals Non-Commercial TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7592219","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592219","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7592219","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.01298-20","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.01298-20","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32847852","host_type":"repository"},{"url":"https://dx.doi.org/10.1128/jvi.01298-20","host_type":""}],"fields_of_study":["Viral-associated cancers and disorders","Ubiquitin and proteasome pathways","Histiocytic Disorders and Treatments","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Cell Line","Epstein-Barr Virus Infections","Gene Expression Regulation, Viral","Herpesvirus 4, Human","Humans","Mutation","Promoter Regions, Genetic","Protein Binding","Protein Domains","Trans-Activators","Ubiquitin","Viral Proteins","Virus Replication"],"mesh_terms":["Protein Domains","Cell Line","Herpesvirus 4, Human","Humans","Mutation","Promoter Regions, Genetic","Protein Binding","Viral Proteins","Virus Replication","Trans-Activators","Gene Expression Regulation, Viral","Epstein-Barr Virus Infections","Ubiquitin"],"keywords":["Lytic cycle","SUMO protein","Ubiquitin","Biology","Epstein–Barr virus","Viral replication","Transactivation","Virus","Gammaherpesvirinae","Phosphorylation","Virology","Viral protein","Cell biology","Herpesviridae","Ubiquitin ligase","Gene","Gene expression","Viral disease","Genetics","Ubiquitination","Epstein-Barr virus","Reactivation","Zta","Lytic Replication","Gene Expression Regulation, Viral","Epstein-Barr Virus Infections","Herpesvirus 4, Human","Virus Replication","Cell Line","Viral Proteins","Protein Domains","Mutation","Trans-Activators","Humans","Promoter Regions, Genetic","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Zero hunger"},{"sdg_number":0,"sdg_label":"Responsible consumption and production"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.19933011.v1","title":"Additional file 1 of TRIM4-mediated ubiquitination of NSP2 restricts porcine reproductive and respiratory syndrome virus proliferation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19933011","title":"Additional file 1 of TRIM4-mediated ubiquitination of NSP2 restricts porcine reproductive and respiratory syndrome virus proliferation","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T09:01:41.290381Z","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":[]}