{"doi":"10.1128/jvi.02045-10","title":"Multiple Interactions between the ESCRT Machinery and Arrestin-Related Proteins: Implications for PPXY-Dependent Budding","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Late domains are short peptide sequences encoded by enveloped viruses to promote the final separation of the nascent virus from the infected cell. These amino acid motifs facilitate viral egress by interacting with components of the ESCRT (endosomal sorting complex required for transport) machinery, ultimately leading to membrane scission by recruiting ESCRT-III to the site of viral budding. PPXY late (L) domains present in viruses such as murine leukemia virus (MLV) or human T-cell leukemia virus type 1 (HTLV-1) access the ESCRT pathway via interaction with HECT ubiquitin ligases (WWP1, WWP2, and Itch). However, the mechanism of ESCRT-III recruitment in this context remains elusive. In this study, we tested the\n            <jats:italic>a</jats:italic>\n            rrestin-\n            <jats:italic>r</jats:italic>\n            elated\n            <jats:italic>t</jats:italic>\n            rafficking (ART) proteins, namely, ARRDC1 (arrestin domain-containing protein 1) to ARRDC4 and TXNIP (thioredoxin-interacting protein), for their ability to function as adaptors between HECT ubiquitin ligases and the core ESCRT machinery in PPXY-dependent budding. We present several lines of evidence in support of such a role: ARTs interact with HECT ubiquitin ligases, and they also exhibit multiple interactions with components of the ESCRT pathway, namely, ALIX and Tsg101, and perhaps with an as yet unidentified factor. Additionally, the ARTs can be recruited to the site of viral budding, and their overexpression results in a PPXY-specific inhibition of MLV budding. Lastly, we show that WWP1 changes the ubiquitination status of ARRDC1, suggesting that the ARTs may provide a platform for ubiquitination in PPXY-dependent budding. Taken together, our results support a model whereby ARTs are involved in PPXY-mediated budding by interacting with HECT ubiquitin ligases and providing several alternative routes for ESCRT-III recruitment.\n          </jats:p>","journal":"Journal of Virology","year":2011,"id":680552,"datarank":0.7335523692332632,"base_score":4.890349128221754,"endowment":4.890349128221754,"self_citation_contribution":0.7335523692332632,"citation_network_contribution":0.0,"self_endowment_contribution":0.7335523692332632,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":132,"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":201621,"name":"Juan Martin-Serrano","orcid":"0000-0002-8183-3914","position":1,"is_corresponding":false},{"id":630507,"name":"Susanne Rauch","orcid":"0009-0008-4587-5384","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Multiple Interactions between the ESCRT Machinery and Arrestin-Related Proteins: Implications for PPXY-Dependent Budding","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Late domains are short peptide sequences encoded by enveloped viruses to promote the final separation of the nascent virus from the infected cell. These amino acid motifs facilitate viral egress by interacting with components of the ESCRT (endosomal sorting complex required for transport) machinery, ultimately leading to membrane scission by recruiting ESCRT-III to the site of viral budding. PPXY late (L) domains present in viruses such as murine leukemia virus (MLV) or human T-cell leukemia virus type 1 (HTLV-1) access the ESCRT pathway via interaction with HECT ubiquitin ligases (WWP1, WWP2, and Itch). However, the mechanism of ESCRT-III recruitment in this context remains elusive. In this study, we tested the\n            <jats:italic>a</jats:italic>\n            rrestin-\n            <jats:italic>r</jats:italic>\n            elated\n            <jats:italic>t</jats:italic>\n            rafficking (ART) proteins, namely, ARRDC1 (arrestin domain-containing protein 1) to ARRDC4 and TXNIP (thioredoxin-interacting protein), for their ability to function as adaptors between HECT ubiquitin ligases and the core ESCRT machinery in PPXY-dependent budding. We present several lines of evidence in support of such a role: ARTs interact with HECT ubiquitin ligases, and they also exhibit multiple interactions with components of the ESCRT pathway, namely, ALIX and Tsg101, and perhaps with an as yet unidentified factor. Additionally, the ARTs can be recruited to the site of viral budding, and their overexpression results in a PPXY-specific inhibition of MLV budding. Lastly, we show that WWP1 changes the ubiquitination status of ARRDC1, suggesting that the ARTs may provide a platform for ubiquitination in PPXY-dependent budding. Taken together, our results support a model whereby ARTs are involved in PPXY-mediated budding by interacting with HECT ubiquitin ligases and providing several alternative routes for ESCRT-III recruitment.\n          </jats:p>","is_dataset_classified":null,"base_score":4.890349128221754,"endowment":4.890349128221754,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21191027","pmcid":"PMC3067843","openalex_id":"https://openalex.org/W2133157618","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"G0802777","title":null}],"total_grants":1,"fwci":4.326,"citation_percentile":0.94990074,"influential_citations":0,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":13},{"year":2014,"count":7},{"year":2015,"count":6},{"year":2016,"count":13},{"year":2017,"count":5},{"year":2018,"count":7},{"year":2019,"count":3},{"year":2020,"count":6},{"year":2021,"count":13},{"year":2022,"count":5},{"year":2023,"count":14},{"year":2024,"count":8},{"year":2025,"count":8},{"year":2026,"count":2}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3067843","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3067843","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02045-10","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.02045-10","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21191027","host_type":"repository"},{"url":"https://kclpure.kcl.ac.uk/portal/en/publications/b3b09da6-a60d-4d95-9893-c4f81a5206db","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","Ubiquitin and proteasome pathways","Endoplasmic Reticulum Stress and Disease","Animals","Arrestins","Carrier Proteins","Cell Line","Endosomal Sorting Complexes Required for Transport","Humans","Immunoprecipitation","Leukemia Virus, Murine","Mice","Protein Interaction Mapping","Two-Hybrid System Techniques","Ubiquitin-Protein Ligases","Virus Release"],"mesh_terms":["Animals","Carrier Proteins","Cell Line","Humans","Leukemia Virus, Murine","Arrestins","Two-Hybrid System Techniques","Protein Interaction Mapping","Ubiquitin-Protein Ligases","Immunoprecipitation","Mice","Endosomal Sorting Complexes Required for Transport","Virus Release"],"keywords":["ESCRT","TSG101","NEDD4","Biology","Ubiquitin","Cell biology","Endosome","Ubiquitin ligase","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T15:27:43.274662Z","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":[]}