{"doi":"10.1210/mend.12.10.0184","title":"Inhibition of Estrogen Receptor Action by the Orphan Receptor SHP (Short Heterodimer Partner)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>SHP (short heterodimer partner) is an unusual orphan receptor that lacks a conventional DNA-binding domain. Previous results have shown that it interacts with several other nuclear hormone receptors, including the retinoid and thyroid hormone receptors, and inhibits their ligand-dependent transcriptional activation. Here we show that SHP also interacts with estrogen receptors and inhibits their function. In mammalian and yeast two-hybrid systems as well as glutathione-S-transferase pull-down assays, SHP interacts specifically with estrogen receptor-α (ERα) in an agonist-dependent manner. The same assay systems using various deletion mutants of SHP map the interaction domain with ERα to the same SHP sequences required for interaction with the nonsteroid hormone receptors such as retinoid X receptor and thyroid hormone receptor. In transient cotransfection assays, SHP inhibits estradiol -dependent activation by ERα by about 5-fold. In contrast, SHP interacts with ERβ independent of ligand and reduces its ability to activate transcription by only 50%. These data suggest that SHP functions to regulate estrogen signaling through a direct interaction with ERα.</jats:p>","journal":"Molecular Endocrinology","year":1998,"id":590492,"datarank":8.16069884750548,"base_score":4.9344739331306915,"endowment":4.9344739331306915,"self_citation_contribution":0.7401710899696038,"citation_network_contribution":7.420527757535875,"self_endowment_contribution":0.7401710899696038,"citer_contribution":7.420527757535875,"corpus_percentile":null,"corpus_rank":null,"citation_count":138,"citer_count":128,"citers_with_citation_signal":122,"citers_with_endowment":122,"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":1510816,"name":"Bettina Hanstein","orcid":null,"position":1,"is_corresponding":false},{"id":443,"name":"Myles Brown","orcid":"0000-0002-8213-1658","position":2,"is_corresponding":false},{"id":323913,"name":"David D. Moore","orcid":"0000-0002-5151-9748","position":3,"is_corresponding":false},{"id":1505134,"name":"Wongi Seol","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inhibition of Estrogen Receptor Action by the Orphan Receptor SHP (Short Heterodimer Partner)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>SHP (short heterodimer partner) is an unusual orphan receptor that lacks a conventional DNA-binding domain. Previous results have shown that it interacts with several other nuclear hormone receptors, including the retinoid and thyroid hormone receptors, and inhibits their ligand-dependent transcriptional activation. Here we show that SHP also interacts with estrogen receptors and inhibits their function. In mammalian and yeast two-hybrid systems as well as glutathione-S-transferase pull-down assays, SHP interacts specifically with estrogen receptor-α (ERα) in an agonist-dependent manner. The same assay systems using various deletion mutants of SHP map the interaction domain with ERα to the same SHP sequences required for interaction with the nonsteroid hormone receptors such as retinoid X receptor and thyroid hormone receptor. In transient cotransfection assays, SHP inhibits estradiol -dependent activation by ERα by about 5-fold. In contrast, SHP interacts with ERβ independent of ligand and reduces its ability to activate transcription by only 50%. These data suggest that SHP functions to regulate estrogen signaling through a direct interaction with ERα.</jats:p>","is_dataset_classified":null,"base_score":4.9344739331306915,"endowment":4.9344739331306915,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9773978","pmcid":null,"openalex_id":"https://openalex.org/W2051777413","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA-57374","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK-46546","title":null}],"total_grants":2,"fwci":5.4592,"citation_percentile":0.95940119,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":5},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2023,"count":1},{"year":2025,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/mend/article-pdf/12/10/1551/10713711/mend1551.pdf","host_type":"journal"},{"url":"https://academic.oup.com/mend/article-pdf/12/10/1551/10713711/mend1551.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/mend/article-pdf/12/10/1551/10713711/mend1551.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/mend.12.10.0184","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9773978","host_type":"repository"}],"fields_of_study":["Estrogen and related hormone effects","Retinoids in leukemia and cellular processes","Genomics, phytochemicals, and oxidative stress","Estradiol","Estrogen Receptor alpha","Humans","Receptors, Cytoplasmic and Nuclear","Receptors, Estrogen","Recombinant Fusion Proteins","Tamoxifen","Transcriptional Activation","Yeasts"],"mesh_terms":["Estradiol","Humans","Receptors, Estrogen","Recombinant Fusion Proteins","Tamoxifen","Yeasts","Transcriptional Activation","Receptors, Cytoplasmic and Nuclear","Estrogen Receptor alpha"],"keywords":["Small heterodimer partner","Estrogen-related receptor gamma","Biology","Estrogen receptor","Nuclear receptor","Thyroid hormone receptor","Retinoid X receptor","Estrogen receptor beta","Thyroid hormone receptor beta","Retinoid X receptor alpha","Cell biology","Receptor","Orphan receptor","Transcription factor","Retinoid X receptor beta","DNA-binding domain","Hormone response element","Hormone receptor","Biochemistry","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T23:17:25.903981Z","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":[]}