{"doi":"10.1016/j.celrep.2012.08.019","title":"Structural Basis for a Reciprocal Regulation between SCF and CSN","abstract":null,"journal":"Cell Reports","year":2012,"id":660397,"datarank":0.7676990718625134,"base_score":5.117993812416755,"endowment":5.117993812416755,"self_citation_contribution":0.7676990718625134,"citation_network_contribution":0.0,"self_endowment_contribution":0.7676990718625134,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":166,"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":1723910,"name":"Daniel C. Scott","orcid":null,"position":1,"is_corresponding":false},{"id":1723911,"name":"Paula C.A. da Fonseca","orcid":null,"position":2,"is_corresponding":false},{"id":1551604,"name":"Anne Schreiber","orcid":null,"position":3,"is_corresponding":false},{"id":1723912,"name":"Julie K. Monda","orcid":null,"position":4,"is_corresponding":false},{"id":1723914,"name":"Brenda A. Schulman","orcid":null,"position":5,"is_corresponding":false},{"id":145729,"name":"Matthias Peter","orcid":null,"position":6,"is_corresponding":false},{"id":1723917,"name":"Edward P. Morris","orcid":null,"position":7,"is_corresponding":false},{"id":1723909,"name":"Radoslav I. Enchev","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural Basis for a Reciprocal Regulation between SCF and CSN","abstract":"Skp1-Cul1-Fbox (SCF) E3 ligases are activated by ligation to the ubiquitin-like protein Nedd8, which is reversed by the deneddylating Cop9 signalosome (CSN). However, CSN also promotes SCF substrate turnover through unknown mechanisms. Through biochemical and electron microscopy analyses, we determined molecular models of CSN complexes with SCF(Skp2/Cks1) and SCF(Fbw7) and found that CSN occludes both SCF functional sites-the catalytic Rbx1-Cul1 C-terminal domain and the substrate receptor. Indeed, CSN binding prevents SCF interactions with E2 enzymes and a ubiquitination substrate, and it inhibits SCF-catalyzed ubiquitin chain formation independent of deneddylation. Importantly, CSN prevents neddylation of the bound cullin, unless binding of a ubiquitination substrate triggers SCF dissociation and neddylation. Taken together, the results provide a model for how reciprocal regulation sensitizes CSN to the SCF assembly state and inhibits a catalytically competent SCF until a ubiquitination substrate drives its own degradation by displacing CSN, thereby promoting cullin neddylation and substrate ubiquitination.","is_dataset_classified":null,"base_score":5.117993812416755,"endowment":5.117993812416755,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22959436","pmcid":"PMC3703508","openalex_id":"https://openalex.org/W1991183072","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA021765","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01GM069530","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM069530-05","title":"Ubiquitin-like Protein Activation and Transfer"},{"funder_name":"Swiss National Science Foundation","grant_id":"141148","title":"Function and regulation of cullin-based E3 ubiquitin-ligases"},{"funder_name":"European Commission","grant_id":"302811","title":"Multimodal Regulation of Cullin-RING Ligases by CSN"},{"funder_name":"European Commission","grant_id":"268930","title":"Regulation of cell growth and division by selective degradation mechanisms"},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":8,"fwci":7.1227,"citation_percentile":0.98071118,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":24},{"year":2014,"count":21},{"year":2015,"count":10},{"year":2016,"count":13},{"year":2017,"count":11},{"year":2018,"count":8},{"year":2019,"count":12},{"year":2020,"count":18},{"year":2021,"count":7},{"year":2022,"count":8},{"year":2023,"count":10},{"year":2024,"count":10},{"year":2025,"count":6},{"year":2026,"count":5}],"oa_status":"gold","license":"CC BY NC ND","oa_locations":[{"url":"https://doi.org/10.1016/j.celrep.2012.08.019","host_type":"journal"},{"url":"https://doi.org/10.1016/j.celrep.2012.08.019","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124712002598?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124712002598?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22959436","host_type":"repository"},{"url":"http://hdl.handle.net/20.500.11850/57706","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3703508","host_type":"repository"},{"url":"https://doaj.org/article/95d27973a68a4db69a2cc1b77c5f3735","host_type":"repository"},{"url":"https://doi.org/10.3929/ethz-b-000057706","host_type":"repository"},{"url":"https://dx.doi.org/10.3929/ethz-b-000057706","host_type":""},{"url":"http://dx.doi.org/10.1016/j.celrep.2012.08.019","host_type":""},{"url":"https://dx.doi.org/10.1016/j.celrep.2012.08.019","host_type":""},{"url":"https://sonar.ch/global/documents/223091","host_type":""}],"fields_of_study":["Ubiquitin and proteasome pathways","Cancer-related Molecular Pathways","Autophagy in Disease and Therapy","0301 basic medicine","0303 health sciences","03 medical and health sciences","Carrier Proteins","Cell Line","Cullin Proteins","Humans","Multienzyme Complexes","Protein Structure, Quaternary","Protein Structure, Tertiary","Proteolysis","SKP Cullin F-Box Protein Ligases","Ubiquitin"],"mesh_terms":["Carrier Proteins","Cell Line","Humans","Multienzyme Complexes","Protein Structure, Tertiary","Protein Structure, Quaternary","Ubiquitin","Cullin Proteins","SKP Cullin F-Box Protein Ligases","Proteolysis"],"keywords":["Neddylation","NEDD8","Ubiquitin","COP9 signalosome","Cullin","Cell biology","Cell division control protein 4","Chemistry","Skp1","F-box protein","Deubiquitinating enzyme","Biochemistry","Biology","Ubiquitin ligase","Enzyme","Protease","SKP Cullin F-Box Protein Ligases","QH301-705.5","Cullin Proteins","Cell Line","Protein Structure, Tertiary","Multienzyme Complexes","Proteolysis","Humans","Biology (General)","Carrier Proteins","Protein Structure, Quaternary"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"emdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T09:07:02.556736Z","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":[]}