{"doi":"10.1096/fasebj.23.1_supplement.94.3","title":"Nuclear receptor coactivators: Regulation of turnover and function","abstract":"<jats:sec>\n                    <jats:label/>\n                    <jats:p>Steroid receptor coactivators, such as the SRC‐family of molecules, amplify nuclear receptor induction of gene expression by modifying promoter chromatin structure and implementing all of the downstream subreactions required for efficient transcription. Induced post‐translational modifications such as phosphorylations 'acivate' the SRC‐3 coactivator by allowing formation of active coactivator multimeric complexes with the receptors. Two regulable sets of co‐coactivator molecules control the degradation of SRC‐3 coactivator. E3 ubiquitin ligases control the lifetime of 'transcriptionally activated SRC‐3' by virtue of a 'ubiquitin transcriptional clock', which begins by a monoubiquitin‐dependent activation and ends via a polyubiquitylatin‐dependent degradation. In contrast, the REGγ proteasomal Cap controls the cellular levels of 'inactive SRC‐3 coactivator' via an ubiquitin‐independent and ATP‐independent mechanism. Turnover of coactivators is additionally regulated by specific kinases, such as atypical PKC, which modify the C‐terminal region of SRC‐3 and prevent the entrance of the coactivator into the 20S proteasome core. Since many coactivators are oncogenes (or tumor suppressors), the mechanisms for controlling their levels are crucial for the regulation of all hormone‐mediated physiological and pathological consequences.</jats:p>\n                  </jats:sec>","journal":"The FASEB Journal","year":2009,"id":23105,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":143045,"name":"Bert W. O'Malley","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24259432","pmcid":null,"openalex_id":"https://openalex.org/W3177216449","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.37918638,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://doi.org/10.1096/fasebj.23.1_supplement.94.3","host_type":"journal"}],"fields_of_study":["Estrogen and related hormone effects","NF-κB Signaling Pathways","Chemokine receptors and signaling","Biology","Medicine"],"mesh_terms":[],"keywords":["Coactivator","Nuclear receptor coactivator 3","Nuclear receptor coactivator 2","Nuclear receptor coactivator 1","Nuclear receptor","Cell biology","Mediator","Proto-oncogene tyrosine-protein kinase Src","Ubiquitin","Transcription factor","Biology","Chemistry","Biochemistry","Signal transduction","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T18:05:16.891916Z","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":[]}