{"doi":"10.1126/science.1079474","title":"Role of EDEM in the Release of Misfolded Glycoproteins from the Calnexin Cycle","abstract":"<jats:p>The mechanisms that determine how folding attempts are interrupted to target folding-incompetent proteins for endoplasmic reticulum–associated degradation (ERAD) are poorly defined. Here the α-mannosidase I–like protein EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. EDEM overexpression resulted in faster release of folding-incompetent proteins from the calnexin cycle and earlier onset of degradation, whereas EDEM down-regulation prolonged folding attempts and delayed ERAD. Up-regulation of EDEM during ER stress may promote cell recovery by clearing the calnexin cycle and by accelerating ERAD of terminally misfolded polypeptides.</jats:p>","journal":"Science","year":2003,"id":38801,"datarank":12.351142789054077,"base_score":6.144185634125646,"endowment":6.144185634125646,"self_citation_contribution":0.921627845118847,"citation_network_contribution":11.42951494393523,"self_endowment_contribution":0.921627845118847,"citer_contribution":11.42951494393523,"corpus_percentile":null,"corpus_rank":null,"citation_count":465,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"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":191867,"name":"Verena Calanca","orcid":null,"position":1,"is_corresponding":false},{"id":191868,"name":"Carmela Galli","orcid":null,"position":2,"is_corresponding":false},{"id":191869,"name":"Paola Lucca","orcid":null,"position":3,"is_corresponding":false},{"id":141786,"name":"Paolo Paganetti","orcid":null,"position":4,"is_corresponding":false},{"id":191866,"name":"Maurizio Molinari","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":6.144185634125646,"endowment":6.144185634125646,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12610306","pmcid":null,"openalex_id":"https://openalex.org/W1964706050","authors":[],"funders":[],"total_grants":0,"fwci":15.839,"citation_percentile":0.99660201,"influential_citations":31,"citation_trend":[{"year":2012,"count":21},{"year":2013,"count":21},{"year":2014,"count":13},{"year":2015,"count":13},{"year":2016,"count":15},{"year":2017,"count":8},{"year":2018,"count":12},{"year":2019,"count":16},{"year":2020,"count":15},{"year":2021,"count":15},{"year":2022,"count":5},{"year":2023,"count":11},{"year":2024,"count":5},{"year":2025,"count":7},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.1079474","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.1079474","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12610306","host_type":"repository"}],"fields_of_study":["Endoplasmic Reticulum Stress and Disease","Transgenic Plants and Applications","Pancreatic function and diabetes","Biology","Medicine","Aspartic Acid Endopeptidases","Calnexin","Cell Line","Down-Regulation","Electrophoresis, Polyacrylamide Gel","Endoplasmic Reticulum","Glycoproteins","Glycosylation","Humans","Kinetics","Membrane Proteins","Molecular Weight","Polysaccharides","Protein Conformation","Protein Folding","RNA Interference","Transfection","Up-Regulation"],"mesh_terms":["Cell Line","Electrophoresis, Polyacrylamide Gel","Endoplasmic Reticulum","Glycoproteins","Glycosylation","Humans","Kinetics","Membrane Proteins","Molecular Weight","Polysaccharides","Protein Conformation","Transfection","Down-Regulation","Up-Regulation","Aspartic Acid Endopeptidases","Protein Folding","RNA Interference","Calnexin"],"keywords":["Calnexin","Endoplasmic-reticulum-associated protein degradation","Endoplasmic reticulum","Protein folding","Glycoprotein","Cell biology","Folding (DSP implementation)","Chemistry","Unfolded protein response","Biology","Biochemistry","Calreticulin"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-11T06:20:36.130419Z","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":[]}