{"doi":"10.1091/mbc.e13-10-0585","title":"Autoregulation of the 26S proteasome by in situ ubiquitination","abstract":"<jats:p>The 26S proteasome degrades ubiquitinated proteins, and proteasomal degradation controls various cellular events. Here we report that the human 26S proteasome is ubiquitinated, by which the ubiquitin receptors Adrm1 and S5a, the ATPase subunit Rpt5, and the deubiquitinating enzyme Uch37 are ubiquitinated in situ by proteasome-associating ubiquitination enzymes. Ubiquitination of these subunits significantly impairs the 26S proteasome's ability to bind, deubiquitinate, and degrade ubiquitinated proteins. Moreover, ubiquitination of the 26S proteasome can be antagonized by proteasome-residing deubiquitinating enzymes, by the binding of polyubiquitin chains, and by certain cellular stress, indicating that proteasome ubiquitination is dynamic and regulated in cells. We propose that in situ ubiquitination of the 26S proteasome regulates its activity, which could function to adjust proteasomal activity in response to the alteration of cellular ubiquitination levels.</jats:p>","journal":"Molecular Biology of the Cell","year":2014,"id":22941,"datarank":3.0614813658639846,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"self_citation_contribution":0.6394019815561974,"citation_network_contribution":2.422079384307787,"self_endowment_contribution":0.6394019815561974,"citer_contribution":2.422079384307787,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":71,"citers_with_citation_signal":66,"citers_with_endowment":66,"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":142588,"name":"Andrea MacFadden","orcid":null,"position":1,"is_corresponding":false},{"id":110360,"name":"Zhiping Wu","orcid":"0000-0002-5554-3681","position":2,"is_corresponding":false},{"id":97162,"name":"Junmin Peng","orcid":"0000-0003-0472-7648","position":3,"is_corresponding":false},{"id":142589,"name":"Chang-Wei Liu","orcid":null,"position":4,"is_corresponding":false},{"id":142587,"name":"Andrew D. Jacobson","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24743594","pmcid":"PMC4055262","openalex_id":"https://openalex.org/W2099095224","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"5R01NS72397","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS072397","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01NS072397-02","title":"Cellular regulation by protein ubiquitination/deubiquitination"}],"total_grants":3,"fwci":3.4143,"citation_percentile":0.93197852,"influential_citations":8,"citation_trend":[{"year":2014,"count":3},{"year":2015,"count":8},{"year":2016,"count":6},{"year":2017,"count":7},{"year":2018,"count":10},{"year":2019,"count":9},{"year":2020,"count":8},{"year":2021,"count":4},{"year":2022,"count":7},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"closed","license":"CC BY NC SA","oa_locations":[{"url":"https://doi.org/10.1091/mbc.e13-10-0585","host_type":"HYBRID"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24743594","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4055262","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4055262","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4055262?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1091/mbc.E13-10-0585","host_type":""},{"url":"https://dx.doi.org/10.1091/mbc.e13-10-0585","host_type":""}],"fields_of_study":["Ubiquitin and proteasome pathways","Autophagy in Disease and Therapy","Genetics and Neurodevelopmental Disorders","Biology","Medicine","0301 basic medicine","0303 health sciences","03 medical and health sciences","HEK293 Cells","Humans","Intracellular Signaling Peptides and Proteins","Membrane Glycoproteins","Oxidative Stress","Polyubiquitin","Proteasome Endopeptidase Complex","Protein Subunits","Proteolysis","RNA-Binding Proteins","Ubiquitin Thiolesterase","Ubiquitin-Conjugating Enzymes","Ubiquitin-Protein Ligases","Ubiquitinated Proteins","Ubiquitination"],"mesh_terms":["Humans","Membrane Glycoproteins","RNA-Binding Proteins","Oxidative Stress","Protein Subunits","Polyubiquitin","Ubiquitin Thiolesterase","Ubiquitin-Conjugating Enzymes","Ubiquitin-Protein Ligases","Proteasome Endopeptidase Complex","Intracellular Signaling Peptides and Proteins","Ubiquitination","Ubiquitinated Proteins","HEK293 Cells","Proteolysis"],"keywords":["Ubiquitin","Deubiquitinating enzyme","Proteasome","Biology","Cell biology","Ubiquitin-conjugating enzyme","F-box protein","Ubiquitin ligase","Protein subunit","Biochemistry","Gene","Proteasome Endopeptidase Complex","Membrane Glycoproteins","Ubiquitin-Protein Ligases","Intracellular Signaling Peptides and Proteins","Ubiquitination","RNA-Binding Proteins","Articles","Ubiquitinated Proteins","Oxidative Stress","Protein Subunits","HEK293 Cells","Proteolysis","Ubiquitin-Conjugating Enzymes","Humans","Polyubiquitin","Ubiquitin Thiolesterase"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T17:10:40.673301Z","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":[]}