{"doi":"10.1074/jbc.m112.448258","title":"The Cyclomodulin Cycle Inhibiting Factor (CIF) Alters Cullin Neddylation Dynamics","abstract":null,"journal":"Journal of Biological Chemistry","year":2013,"id":603274,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"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":1547565,"name":"Julia I. Toth","orcid":null,"position":1,"is_corresponding":false},{"id":915912,"name":"Matthew D. Petroski","orcid":null,"position":2,"is_corresponding":false},{"id":114249,"name":"Tasha B. Toro","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Cyclomodulin Cycle Inhibiting Factor (CIF) Alters Cullin Neddylation Dynamics","abstract":"The bacterial effector protein cycle inhibiting factor (CIF) converts glutamine 40 of NEDD8 to glutamate (Q40E), causing cytopathic effects and inhibiting cell proliferation. Although these have been attributed to blocking the functions of cullin-RING ubiquitin ligases, how CIF modulates NEDD8-dependent signaling is unclear. Here we use conditional NEDD8-dependent yeast to explore the effects of CIF on cullin neddylation. Although CIF causes cullin deneddylation and the generation of free NEDD8 Q40E, inhibiting the COP9 signalosome (CSN) allows Q40E to form only on NEDD8 attached to cullins. In the presence of the CSN, NEDD8 Q40E is removed from cullins more rapidly than NEDD8, leading to a decrease in steady-state cullin neddylation. As NEDD8 Q40E is competent for cullin conjugation in the absence of functional CSN and with overexpression of the NEDD8 ligase Dcn1, our data are consistent with NEDD8 deamidation causing enhanced deneddylation of cullins by the CSN. This leads to a dramatic change in the extent of activated cullin-RING ubiquitin ligases. Background: CIF converts NEDD8 glutamine 40 to glutamate, inactivating cullin-RING ubiquitin ligases (CRLs). Results: CIF deamidates NEDD8 covalently attached to cullins, leading to NEDD8 system inhibition. Conclusion: CIF directly inactivates neddylated CRL complexes and, subsequently, interferes with NEDD8 system function. Significance: This newly described posttranslational mechanism highlights how a subtle amino acid change in a protein can have far-reaching and amplified biological effects.","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23589306","pmcid":"PMC3663497","openalex_id":"https://openalex.org/W2034625176","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"5 T32 CA121949","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA121949","title":null}],"total_grants":2,"fwci":1.2381,"citation_percentile":0.78262361,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":2},{"year":2015,"count":2},{"year":2016,"count":3},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1074/jbc.m112.448258","host_type":"journal"},{"url":"https://doi.org/10.1074/jbc.m112.448258","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820460132?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820460132?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M112.448258","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23589306","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3663497","host_type":"repository"}],"fields_of_study":["Ubiquitin and proteasome pathways","Endoplasmic Reticulum Stress and Disease","RNA modifications and cancer","Bacterial Proteins","COP9 Signalosome Complex","Cullin Proteins","Glutamic Acid","Glutamine","Humans","Multiprotein Complexes","NEDD8 Protein","Peptide Hydrolases","Protein Processing, Post-Translational","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Ubiquitin-Protein Ligases","Ubiquitins"],"mesh_terms":["COP9 Signalosome Complex","NEDD8 Protein","Bacterial Proteins","Glutamine","Humans","Peptide Hydrolases","Protein Processing, Post-Translational","Saccharomyces cerevisiae","Ubiquitins","Glutamic Acid","Saccharomyces cerevisiae Proteins","Ubiquitin-Protein Ligases","Cullin Proteins","Multiprotein Complexes"],"keywords":["Cullin","Neddylation","Chemistry","Cell biology","NEDD8","Dynamics (music)","Biochemistry","Biology","Ubiquitin","Physics","Ubiquitin ligase","Signal transduction","Ubiquitination","Yeast","ubiquitin-like proteins","Cif","Cullin-ring Ubiquitin Ligases"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T21:29:39.621874Z","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":[]}