{"doi":"10.1073/pnas.092043399","title":"Interactions that determine the assembly of a retinoid X receptor/corepressor complex","abstract":"<jats:p>The retinoid X receptor (RXR) is a key regulator in multiple signaling pathways because it can form either a homodimer with itself or a heterodimer with members of the class I nuclear receptors. The RXR-containing dimers regulate transcription by recruiting coactivators or corepressors to the target promoters. The binding of coactivators to RXR is mediated through a hydrophobic pocket formed in part by the C-terminal activation helix (AF-2). However, little is known about interactions of corepressors with RXR and its roles in transcriptional repression. Here we show that the repression activity of RXR correlates with its binding to the corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT). This intrinsic repression activity is masked by the AF-2 helix, which antagonizes SMRT binding. Inhibition of SMRT binding by the AF-2 helix requires specific amino acid sequences and the helical structure. Furthermore, the SMRT-binding site on RXR is independent of helix 11 but overlaps with the coactivator-binding pocket. On the basis of these results, we propose a structural model to help understand the molecular mechanism of corepressor recruitment by RXR.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2002,"id":22833,"datarank":3.03668727557023,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":2.4498838247560077,"self_endowment_contribution":0.586803450814222,"citer_contribution":2.4498838247560077,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":46,"citers_with_citation_signal":43,"citers_with_endowment":43,"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":142249,"name":"Xiaofang Yang","orcid":null,"position":1,"is_corresponding":false},{"id":142250,"name":"Aihua Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":142251,"name":"Millard H. Lambert","orcid":null,"position":3,"is_corresponding":false},{"id":15834,"name":"Hui Li","orcid":"0000-0002-7879-1792","position":4,"is_corresponding":false},{"id":112933,"name":"H. Eric Xu","orcid":"0000-0002-6829-8144","position":5,"is_corresponding":false},{"id":142252,"name":"J. Don Chen","orcid":null,"position":6,"is_corresponding":false},{"id":142248,"name":"Jagadish C. Ghosh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11972046","pmcid":"PMC122864","openalex_id":"https://openalex.org/W2007204546","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK52542","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK52888","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK052888","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK052542","title":null}],"total_grants":4,"fwci":1.8402,"citation_percentile":0.84724618,"influential_citations":2,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":3},{"year":2014,"count":1},{"year":2016,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.092043399","host_type":"journal"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.092043399","host_type":"BRONZE"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.092043399","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.092043399","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.092043399","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11972046","host_type":"repository"},{"url":"https://escholarship.umassmed.edu/oapubs/1779","host_type":"repository"},{"url":"https://scholarship.libraries.rutgers.edu/esploro/outputs/journalArticle/Interactions-that-determine-the-assembly-of/991031758029404646","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122864","host_type":"repository"}],"fields_of_study":["Retinoids in leukemia and cellular processes","Estrogen and related hormone effects","Reproductive System and Pregnancy","Biology","Medicine","Amino Acid Sequence","Binding Sites","Cell Line","Cell Nucleus","DNA","DNA-Binding Proteins","Dimerization","Glutathione Transferase","Humans","Models, Genetic","Models, Molecular","Molecular Sequence Data","Mutation","Nuclear Receptor Co-Repressor 2","Plasmids","Protein Binding","Protein Structure, Secondary","Protein Structure, Tertiary","Receptors, Retinoic Acid","Recombinant Fusion Proteins","Repressor Proteins","Retinoid X Receptors","Sequence Homology, Amino Acid","Transcription Factors","Transcription, Genetic","Transfection"],"mesh_terms":["Amino Acid Sequence","Binding Sites","Cell Line","Cell Nucleus","DNA","DNA-Binding Proteins","Glutathione Transferase","Humans","Models, Genetic","Models, Molecular","Molecular Sequence Data","Mutation","Plasmids","Protein Binding","Recombinant Fusion Proteins","Repressor Proteins","Transcription Factors","Transcription, Genetic","Transfection","Sequence Homology, Amino Acid","Protein Structure, Secondary","Protein Structure, Tertiary","Receptors, Retinoic Acid","Dimerization","Retinoid X Receptors","Nuclear Receptor Co-Repressor 2"],"keywords":["Corepressor","Coactivator","Retinoid X receptor","Nuclear receptor","Thyroid hormone receptor","Psychological repression","Cell biology","Transcription factor","Biology","Biochemistry","Chemistry","Receptor","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T16:34:11.777828Z","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":[]}