{"doi":"10.1371/journal.pone.0012683","title":"Interaction of the TNFR-Receptor Associated Factor TRAF1 with I-Kappa B Kinase-2 and TRAF2 Indicates a Regulatory Function for NF-Kappa B Signaling","abstract":null,"journal":"PLoS ONE","year":2010,"id":690150,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"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":179572,"name":"Andreas Birbach","orcid":null,"position":1,"is_corresponding":false},{"id":1803035,"name":"Rainer de Martin","orcid":null,"position":2,"is_corresponding":false},{"id":179571,"name":"Johannes A. Schmid","orcid":null,"position":3,"is_corresponding":false},{"id":1803034,"name":"Kalsoom Sughra","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Interaction of the TNFR-Receptor Associated Factor TRAF1 with I-Kappa B Kinase-2 and TRAF2 Indicates a Regulatory Function for NF-Kappa B Signaling","abstract":"BACKGROUND: I-kappa B kinase 2 (IKK2 or IKK-beta) is one of the most crucial signaling kinases for activation of NF-kappa B, a transcription factor that is important for inflammation, cell survival and differentiation. Since many NF-kappa B activating pathways converge at the level of IKK2, molecular interactions of this kinase are pivotal for regulation of NF-kappa B signaling. METHODOLOGY/PRINCIPAL FINDINGS: We searched for proteins interacting with IKK2 using the C-terminal part (amino acids 466-756) as bait in a yeast two-hybrid system and identified the N-terminal part (amino acids 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner. The interaction was confirmed in human cells by mammalian two-hybrid and coimmunoprecipitation experiments. The IKK2/TRAF1 interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling. Reporter gene and kinase assays using ectopic expression of TRAF1 indicated that it can both activate and inhibit IKK2 and NF-kappa B. Co-expression of fluorescently tagged TRAF1 and TRAF2 at different ratios implied that TRAF1 can affect clustering and presumably the activating function of TRAF2 in a dose dependent manner. CONCLUSIONS/SIGNIFICANCE: The observation that TRAF1 can either activate or inhibit the NF-kappa B pathway and the fact that it influences the oligomerization of TRAF2 indicates that relative levels of IKK2, TRAF1 and TRAF2 may be important for regulation of NF-kappa B activity. Since TRAF1 is an NF-kappa B induced gene, it might act as a feedback effector molecule.","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20856938","pmcid":"PMC2938345","openalex_id":"https://openalex.org/W1983007681","authors":[],"funders":[{"funder_name":"Austrian Science Fund FWF","grant_id":"P 21919","title":"Inflammatory signaling in prostate tumorigenesis"},{"funder_name":"Austrian Science Fund (FWF)","grant_id":"P 19217","title":"Regulatory feedback mechanisms in endothelial cells"}],"total_grants":2,"fwci":0.5141,"citation_percentile":0.67763713,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":2},{"year":2014,"count":5},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":1},{"year":2021,"count":2},{"year":2022,"count":6},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012683&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012683&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0012683","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0012683","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20856938","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2938345","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.350.9847","host_type":""},{"url":"https://doaj.org/article/e535309dbe7243d09dac91b9991d971d","host_type":"repository"},{"url":"https://figshare.com/articles/Interaction_of_the_TNFR_Receptor_Associated_Factor_TRAF1_with_I_Kappa_B_Kinase_2_and_TRAF2_Indicates_a_Regulatory_Function_for_NF_Kappa_B_Signaling/141815","host_type":"repository"},{"url":"http://precedings.nature.com/documents/4153/version/2","host_type":"journal"},{"url":"https://europepmc.org/articles/PMC2938345","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2938345?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1038/npre.2010.4153.2","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pone.0012683","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0012683","host_type":""},{"url":"https://dx.doi.org/10.1038/npre.2010.4153.2","host_type":""},{"url":"http://hdl.handle.net/10101/npre.2010.4153.2","host_type":""}],"fields_of_study":["NF-κB Signaling Pathways","Cell death mechanisms and regulation","Bone Metabolism and Diseases","0301 basic medicine","0303 health sciences","03 medical and health sciences","HEK293 Cells","HeLa Cells","Humans","I-kappa B Kinase","NF-kappa B","Protein Binding","Protein Structure, Tertiary","Signal Transduction","TNF Receptor-Associated Factor 1","TNF Receptor-Associated Factor 2"],"mesh_terms":["HeLa Cells","Humans","Protein Binding","Signal Transduction","NF-kappa B","Protein Structure, Tertiary","TNF Receptor-Associated Factor 1","TNF Receptor-Associated Factor 2","I-kappa B Kinase","HEK293 Cells","Hela Cells"],"keywords":["TRAF2","IκB kinase","NFKB1","Kinase","Cell biology","Biology","Signal transduction","NF-κB","Transcription factor","Cancer research","Receptor","Biochemistry","Gene","Tumor necrosis factor receptor","Science","Immunology","Q","R","NF-kappa B","TNF Receptor-Associated Factor 2","TNF Receptor-Associated Factor 1","I-kappa B Kinase","Protein Structure, Tertiary","HEK293 Cells","Molecular Cell Biology","Medicine","Humans","Research Article","HeLa Cells","Protein Binding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-22T23:36:45.778227Z","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":[]}