{"doi":"10.1128/jvi.00953-08","title":"Ectromelia Virus Encodes a Novel Family of F-Box Proteins That Interact with the SCF Complex","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Poxviruses are notorious for encoding multiple proteins that regulate cellular signaling pathways, including the ubiquitin-proteasome system. Bioinformatics indicated that ectromelia virus, the causative agent of lethal mousepox, encoded four proteins, EVM002, EVM005, EVM154, and EVM165, containing putative F-box domains. In contrast to cellular F-box proteins, the ectromelia virus proteins contain C-terminal F-box domains in conjunction with N-terminal ankyrin repeats, a combination that has not been previously reported for cellular proteins. These observations suggested that the ectromelia virus F-box proteins interact with SCF (\n            <jats:italic>S</jats:italic>\n            kp1,\n            <jats:italic>c</jats:italic>\n            ullin-1, and\n            <jats:italic>F</jats:italic>\n            -box) ubiquitin ligases. We focused our studies on EVM005, since this protein had only one ortholog in cowpox virus. Using mass spectrometry, we identified cullin-1 as a binding partner for EVM005, and this interaction was confirmed by overexpression of hemagglutinin (HA)-cullin-1. During infection, Flag-EVM005 and HA-cullin-1 colocalized to distinct cellular bodies. Significantly, EVM005 coprecipitated with endogenous Skp1, cullin-1, and Roc1 and associated with conjugated ubiquitin, suggesting that EVM005 interacted with the components of a functional ubiquitin ligase. Interaction of EVM005 with cullin-1 and Skp1 was abolished upon deletion of the F-box, indicating that the F-box played a crucial role in interaction with the SCF complex. Additionally, EVM002 and EVM154 interacted with Skp1 and conjugated ubiquitin, suggesting that ectromelia virus encodes multiple F-box-containing proteins that regulate the SCF complex. Our results indicate that ectromelia virus has evolved multiple proteins that interact with the SCF complex.\n          </jats:p>","journal":"Journal of Virology","year":2008,"id":610816,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":1554404,"name":"Brianne Couturier","orcid":null,"position":1,"is_corresponding":false},{"id":63630,"name":"Yue Xiong","orcid":"0000-0003-2744-6566","position":2,"is_corresponding":false},{"id":1554408,"name":"Michele Barry","orcid":null,"position":3,"is_corresponding":false},{"id":1554405,"name":"Nick van Buuren","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ectromelia Virus Encodes a Novel Family of F-Box Proteins That Interact with the SCF Complex","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Poxviruses are notorious for encoding multiple proteins that regulate cellular signaling pathways, including the ubiquitin-proteasome system. Bioinformatics indicated that ectromelia virus, the causative agent of lethal mousepox, encoded four proteins, EVM002, EVM005, EVM154, and EVM165, containing putative F-box domains. In contrast to cellular F-box proteins, the ectromelia virus proteins contain C-terminal F-box domains in conjunction with N-terminal ankyrin repeats, a combination that has not been previously reported for cellular proteins. These observations suggested that the ectromelia virus F-box proteins interact with SCF (\n            <jats:italic>S</jats:italic>\n            kp1,\n            <jats:italic>c</jats:italic>\n            ullin-1, and\n            <jats:italic>F</jats:italic>\n            -box) ubiquitin ligases. We focused our studies on EVM005, since this protein had only one ortholog in cowpox virus. Using mass spectrometry, we identified cullin-1 as a binding partner for EVM005, and this interaction was confirmed by overexpression of hemagglutinin (HA)-cullin-1. During infection, Flag-EVM005 and HA-cullin-1 colocalized to distinct cellular bodies. Significantly, EVM005 coprecipitated with endogenous Skp1, cullin-1, and Roc1 and associated with conjugated ubiquitin, suggesting that EVM005 interacted with the components of a functional ubiquitin ligase. Interaction of EVM005 with cullin-1 and Skp1 was abolished upon deletion of the F-box, indicating that the F-box played a crucial role in interaction with the SCF complex. Additionally, EVM002 and EVM154 interacted with Skp1 and conjugated ubiquitin, suggesting that ectromelia virus encodes multiple F-box-containing proteins that regulate the SCF complex. Our results indicate that ectromelia virus has evolved multiple proteins that interact with the SCF complex.\n          </jats:p>","is_dataset_classified":null,"base_score":3.784189633918261,"endowment":3.784189633918261,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18684824","pmcid":"PMC2566254","openalex_id":"https://openalex.org/W2039143141","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM067113","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM067113","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":4,"fwci":1.6956,"citation_percentile":0.84006916,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":3},{"year":2014,"count":7},{"year":2015,"count":5},{"year":2016,"count":1},{"year":2018,"count":1},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2024,"count":1}],"oa_status":"closed","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.00953-08","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00953-08","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18684824","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2566254","host_type":"repository"}],"fields_of_study":["Poxvirus research and outbreaks","Virus-based gene therapy research","Ubiquitin and proteasome pathways","Amino Acid Sequence","Animals","Cell Line","Ectromelia virus","Ectromelia, Infectious","F-Box Proteins","Humans","Mice","Molecular Sequence Data","Protein Binding","SKP Cullin F-Box Protein Ligases","Sequence Alignment","Ubiquitins","Viral Proteins"],"mesh_terms":["Amino Acid Sequence","Animals","Cell Line","Ectromelia virus","Ectromelia, Infectious","Humans","Molecular Sequence Data","Protein Binding","Ubiquitins","Viral Proteins","Sequence Alignment","F-Box Proteins","SKP Cullin F-Box Protein Ligases","Mice"],"keywords":["Biology","Ectromelia virus","Ectromelia","Genetics","Virus","Virology","Computational biology","Cell biology","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T11:40:22.747502Z","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":[]}