{"doi":"10.15252/embj.2021109566","title":"A heterotypic assembly mechanism regulates CHIP E3 ligase activity","abstract":"CHIP (C-terminus of Hsc70-interacting protein) and its worm ortholog CHN-1 are E3 ubiquitin ligases that link the chaperone system with the ubiquitin-proteasome system (UPS). CHN-1 can cooperate with UFD-2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high processivity of this E3s set has remained obscure. Here, we studied the molecular mechanism and function of the CHN-1-UFD-2 complex in Caenorhabditis elegans. Our data show that UFD-2 binding promotes the cooperation between CHN-1 and ubiquitin-conjugating E2 enzymes by stabilizing the CHN-1 U-box dimer. However, HSP70/HSP-1 chaperone outcompetes UFD-2 for CHN-1 binding, thereby promoting a shift to the autoinhibited CHN-1 state by acting on a conserved residue in its U-box domain. The interaction with UFD-2 enables CHN-1 to efficiently ubiquitylate and regulate S-adenosylhomocysteinase (AHCY-1), a key enzyme in the S-adenosylmethionine (SAM) regeneration cycle, which is essential for SAM-dependent methylation. Our results define the molecular mechanism underlying the synergistic cooperation of CHN-1 and UFD-2 in substrate ubiquitylation.","journal":"The EMBO Journal","year":2022,"id":269053,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":931777,"name":"Pankaj Thapa","orcid":"0000-0001-5536-1768","position":1,"is_corresponding":false},{"id":575036,"name":"Ulises Santiago","orcid":"0000-0003-2259-5984","position":2,"is_corresponding":false},{"id":582417,"name":"Nilesh Shanmugam","orcid":"0000-0002-6813-115X","position":3,"is_corresponding":false},{"id":582937,"name":"Katarzyna Banasiak","orcid":null,"position":4,"is_corresponding":false},{"id":931778,"name":"Katarzyna Dąbrowska","orcid":"0000-0001-7833-0374","position":5,"is_corresponding":false},{"id":254805,"name":"Hendrik Nolte","orcid":"0000-0003-1560-5099","position":6,"is_corresponding":false},{"id":931779,"name":"Natalia A. Szulc","orcid":"0000-0002-2991-3634","position":7,"is_corresponding":false},{"id":931780,"name":"Rose M. Gathungu","orcid":"0000-0002-5552-2565","position":8,"is_corresponding":false},{"id":873822,"name":"Dominik Cysewski","orcid":"0000-0001-6206-0672","position":9,"is_corresponding":false},{"id":470973,"name":"Marcus Krüger","orcid":"0000-0002-5846-6941","position":10,"is_corresponding":false},{"id":383922,"name":"Michał Dadlez","orcid":"0000-0001-8811-5176","position":11,"is_corresponding":false},{"id":415758,"name":"Marcin Nowotny","orcid":"0000-0001-8632-0977","position":12,"is_corresponding":false},{"id":256292,"name":"Carlos J. Camacho","orcid":"0000-0003-1741-8529","position":13,"is_corresponding":false},{"id":337138,"name":"Thorsten Hoppe","orcid":"0000-0002-4734-9352","position":14,"is_corresponding":false},{"id":457108,"name":"Wojciech Pokrzywa","orcid":"0000-0002-5110-4462","position":15,"is_corresponding":false},{"id":931776,"name":"Aniruddha Das","orcid":"0000-0002-7704-3573","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T00:27:18.142851Z","pmid":"35762422","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":[]}