{"doi":"10.1073/pnas.96.16.9124","title":"Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism","abstract":"<jats:p>\n            Ubiquitin-dependent degradation of regulatory proteins controls many cellular processes, including cell cycle progression, morphogenesis, and signal transduction. Skp1p-cullin-F-box protein (SCF) complexes are ubiquitin ligases composed of a core complex including Skp1p, Cdc53p, one of multiple F-box proteins that are thought to provide substrate specificity to the complex, and the ubiquitin-conjugating enzyme, Cdc34p. It is not understood how SCF complexes are regulated and how physiological conditions alter their levels. Here we show that three F-box proteins, Grr1p, Cdc4p, and Met30p, are unstable components of the SCF, and are themselves degraded in a ubiquitin- and proteasome-dependent manner\n            <jats:italic>in vivo</jats:italic>\n            . Ubiquitination requires all the core components of the SCF and an intact F-box, suggesting that ubiquitination occurs within the SCF complex by an autocatalytic mechanism. Cdc4p and Grr1p are intrinsically unstable, and their steady-state levels did not fluctuate through the cell cycle. Taken together, our results suggest that ubiquitin-dependent degradation of F-box proteins allows rapid switching among multiple SCF complexes, thereby enabling cells to adapt quickly to changing physiological conditions and progression through different phases of the cell cycle.\n          </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1999,"id":24122,"datarank":14.297663699870137,"base_score":5.572154032177765,"endowment":5.572154032177765,"self_citation_contribution":0.8358231048266649,"citation_network_contribution":13.461840595043473,"self_endowment_contribution":0.8358231048266649,"citer_contribution":13.461840595043473,"corpus_percentile":null,"corpus_rank":null,"citation_count":262,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":145729,"name":"Matthias Peter","orcid":null,"position":1,"is_corresponding":false},{"id":145728,"name":"Jean-Marc Galan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.572154032177765,"endowment":5.572154032177765,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10430906","pmcid":"PMC17743","openalex_id":"https://openalex.org/W2079760361","authors":[],"funders":[],"total_grants":0,"fwci":5.0757,"citation_percentile":0.9609531,"influential_citations":14,"citation_trend":[{"year":2012,"count":13},{"year":2013,"count":13},{"year":2014,"count":9},{"year":2015,"count":12},{"year":2016,"count":4},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":10},{"year":2020,"count":3},{"year":2021,"count":6},{"year":2022,"count":5},{"year":2023,"count":7},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc17743?pdf=render","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.96.16.9124","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.96.16.9124","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10430906","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC17743","host_type":"repository"},{"url":"https://iris.unil.ch/handle/iris/35458","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/17743","host_type":"repository"},{"url":"https://serval.unil.ch/notice/serval:BIB_12412","host_type":"repository"}],"fields_of_study":["Ubiquitin and proteasome pathways","Autophagy in Disease and Therapy","Endoplasmic Reticulum Stress and Disease","Biology","Medicine","Catalysis","Cell Cycle","Cell Cycle Proteins","F-Box Proteins","Fungal Proteins","Genotype","Peptide Synthases","Repressor Proteins","SKP Cullin F-Box Protein Ligases","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Substrate Specificity","Trans-Activators","Ubiquitin-Protein Ligase Complexes","Ubiquitin-Protein Ligases","Ubiquitins"],"mesh_terms":["Catalysis","Cell Cycle","Fungal Proteins","Genotype","Peptide Synthases","Repressor Proteins","Saccharomyces cerevisiae","Substrate Specificity","Ubiquitins","Trans-Activators","Cell Cycle Proteins","Saccharomyces cerevisiae Proteins","Ubiquitin-Protein Ligase Complexes","Ubiquitin-Protein Ligases","F-Box Proteins","SKP Cullin F-Box Protein Ligases"],"keywords":["F-box protein","Ubiquitin","Ubiquitin-conjugating enzyme","Ubiquitin-Protein Ligases","Cell division control protein 4","Cell biology","Proteasome","Protein degradation","Ubiquitin ligase","Biology","Ubiquitins","Biochemistry","Chemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T21:33:34.730958Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}