{"doi":"10.1074/jbc.m113.506790","title":"Characterizing WW Domain Interactions of Tumor Suppressor WWOX Reveals Its Association with Multiprotein Networks","abstract":null,"journal":"Journal of Biological Chemistry","year":2014,"id":600024,"datarank":0.6814942173405006,"base_score":4.543294782270004,"endowment":4.543294782270004,"self_citation_contribution":0.6814942173405006,"citation_network_contribution":0.0,"self_endowment_contribution":0.6814942173405006,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":93,"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":1538037,"name":"Tomer Bar-Mag","orcid":null,"position":1,"is_corresponding":false},{"id":1538038,"name":"Haiming Huang","orcid":null,"position":2,"is_corresponding":false},{"id":1538039,"name":"TaeHyung Kim","orcid":null,"position":3,"is_corresponding":false},{"id":1183624,"name":"Zaidoun Salah","orcid":null,"position":4,"is_corresponding":false},{"id":1183254,"name":"Suhaib K. Abdeen","orcid":"0009-0008-6787-1069","position":5,"is_corresponding":false},{"id":272201,"name":"Marius Sudol","orcid":"0000-0003-3051-6406","position":6,"is_corresponding":false},{"id":1538041,"name":"Dana Reichmann","orcid":null,"position":7,"is_corresponding":false},{"id":1538042,"name":"Sachdev Sidhu","orcid":null,"position":8,"is_corresponding":false},{"id":454358,"name":"Philip M. Kim","orcid":"0000-0003-3683-152X","position":9,"is_corresponding":false},{"id":3225,"name":"Rami I. Aqeilan","orcid":"0000-0002-6034-023X","position":10,"is_corresponding":false},{"id":269453,"name":"Mohammad Abu-Odeh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Characterizing WW Domain Interactions of Tumor Suppressor WWOX Reveals Its Association with Multiprotein Networks","abstract":"WW domains are small modules present in regulatory and signaling proteins that mediate specific protein-protein interactions. The WW domain-containing oxidoreductase (WWOX) encodes a 46-kDa tumor suppressor that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase domain. Based on its ligand recognition motifs, the WW domain family is classified into four groups. The largest one, to which WWOX belongs, recognizes ligands with a PPXY motif. To pursue the functional properties of the WW domains of WWOX, we employed mass spectrometry and phage display experiments to identify putative WWOX-interacting partners. Our analysis revealed that the first WW (WW1) domain of WWOX is the main functional interacting domain. Furthermore, our study uncovered well known and new PPXY-WW1-interacting partners and shed light on novel LPXY-WW1-interacting partners of WWOX. Many of these proteins are components of multiprotein complexes involved in molecular processes, including transcription, RNA processing, tight junction, and metabolism. By utilizing GST pull-down and immunoprecipitation assays, we validated that WWOX is a substrate of the E3 ubiquitin ligase ITCH, which contains two LPXY motifs. We found that ITCH mediates Lys-63-linked polyubiquitination of WWOX, leading to its nuclear localization and increased cell death. Our data suggest that the WW1 domain of WWOX provides a versatile platform that links WWOX with individual proteins associated with physiologically important networks.","is_dataset_classified":null,"base_score":4.543294782270004,"endowment":4.543294782270004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24550385","pmcid":"PMC3979411","openalex_id":"https://openalex.org/W1971294322","authors":[],"funders":[],"total_grants":0,"fwci":5.0689,"citation_percentile":0.9638966,"influential_citations":0,"citation_trend":[{"year":2014,"count":12},{"year":2015,"count":17},{"year":2016,"count":6},{"year":2017,"count":4},{"year":2018,"count":7},{"year":2019,"count":8},{"year":2020,"count":9},{"year":2021,"count":13},{"year":2022,"count":7},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820419647/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820419647/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820419647?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820419647?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M113.506790","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m113.506790","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24550385","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3979411","host_type":"repository"}],"fields_of_study":["Ubiquitin and proteasome pathways","Genetics and Neurodevelopmental Disorders","Cancer Mechanisms and Therapy","Amino Acid Motifs","HEK293 Cells","Humans","Oxidoreductases","Peptide Library","Protein Binding","Protein Structure, Tertiary","Recombinant Fusion Proteins","Tumor Suppressor Proteins","Ubiquitination","WW Domain-Containing Oxidoreductase"],"mesh_terms":["WW Domain-Containing Oxidoreductase","Humans","Oxidoreductases","Protein Binding","Recombinant Fusion Proteins","Protein Structure, Tertiary","Peptide Library","Amino Acid Motifs","Tumor Suppressor Proteins","Ubiquitination","HEK293 Cells"],"keywords":["WWOX","WW domain","Ubiquitin ligase","Suppressor","Immunoprecipitation","SUMO protein","Biology","Cell biology","Ubiquitin","Computational biology","Genetics","Gene","Ubiquitination","Tumor suppressor gene","mass spectrometry (MS)","E3 ubiquitin ligase","protein-protein interactions","Itch"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T12:00:53.662981Z","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":[]}