{"doi":"10.1530/joe-16-0485","title":"Jab1 is a T2-dependent coactivator or a T3-dependent corepressor of TRB1-mediated gene regulation","abstract":"<jats:p>Thyroid hormones (THs) induce pleiotropic effects in vertebrates, mainly through the activation or repression of gene expression. These mechanisms involve thyroid hormone binding to thyroid hormone receptors, an event that is followed by the sequential recruitment of coactivator or corepressor proteins, which in turn modify the rate of transcription. In the present study, we looked for specific coregulators recruited by the long isoform of the teleostean thyroid hormone receptor beta 1 (L-Trb1) when bound to the bioactive TH, 3,5-T<jats:sub>2</jats:sub> (T<jats:sub>2</jats:sub>). We found that jun activation domain-binding protein1 (Jab1) interacts with L-Trb1 + T<jats:sub>2</jats:sub> complex. Using both the teleostean and human TRB1 isoforms, we characterized the Jab1–TRB1 by yeast two-hybrid, pull-down and transactivation assays. Our results showed that the TRB1–Jab1 interaction was ligand dependent and involved the single Jab1 nuclear receptor box, as well as the ligand-binding and N-terminal domains of TRB1. We also provide evidence of ligand-dependent, dual coregulatory properties of Jab1. Indeed, when T<jats:sub>2</jats:sub> is bound to L-Trb1 or hTRB1, Jab1 acts as a coactivator of transcription, whereas it has corepressor activity when interacting with the T<jats:sub>3</jats:sub>-bound S-Trb1 or hTRB1. These mechanisms could explain some of the pleiotropic actions exerted by THs to regulate diverse biological processes.</jats:p>","journal":"Journal of Endocrinology","year":2017,"id":24703,"datarank":0.31785974030634107,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.025973217948044046,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.025973217948044046,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"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":147426,"name":"Arturo Mendoza","orcid":null,"position":1,"is_corresponding":false},{"id":147427,"name":"Alfonso León-del-Río","orcid":null,"position":2,"is_corresponding":false},{"id":147428,"name":"Aurea Orozco","orcid":null,"position":3,"is_corresponding":false},{"id":147425,"name":"Gabriela Hernández-Puga","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28053002","pmcid":null,"openalex_id":"https://openalex.org/W2570738281","authors":[],"funders":[],"total_grants":0,"fwci":1.0209,"citation_percentile":0.76893339,"influential_citations":0,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://joe.bioscientifica.com/downloadpdf/journals/joe/232/3/451.pdf","host_type":"journal"},{"url":"https://doi.org/10.1530/joe-16-0485","host_type":"BRONZE"},{"url":"https://joe.bioscientifica.com/downloadpdf/journals/joe/232/3/451.pdf","host_type":"publisher"},{"url":"https://joe.bioscientifica.com/view/journals/joe/232/3/451.xml","host_type":"publisher"},{"url":"https://joe.bioscientifica.com/downloadpdf/journals/joe/232/3/451.xml","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28053002","host_type":"repository"}],"fields_of_study":["Thyroid Disorders and Treatments","Retinoids in leukemia and cellular processes","interferon and immune responses","Chemistry","Medicine","Biology","Animals","COP9 Signalosome Complex","Cell Line","Dose-Response Relationship, Drug","Gene Expression Regulation","Intracellular Signaling Peptides and Proteins","Proteins","Rats","Receptors, Thyroid Hormone","Thyroid Hormone Receptors beta","Thyroid Hormones"],"mesh_terms":["COP9 Signalosome Complex","Animals","Cell Line","Dose-Response Relationship, Drug","Gene Expression Regulation","Proteins","Receptors, Thyroid Hormone","Thyroid Hormones","Thyroid Hormone Receptors beta","Intracellular Signaling Peptides and Proteins","Rats"],"keywords":["Corepressor","Coactivator","Transactivation","Thyroid hormone receptor","Nuclear receptor coactivator 3","Nuclear receptor","Gene isoform","Psychological repression","Biology","Transcription factor","Cell biology","Repressor","Receptor","Thyroid hormone receptor beta","Hormone","Endocrinology","Internal medicine","Gene expression","Hormone receptor","Gene","Biochemistry","Genetics","Medicine","JAB1","coregulator","3, 5-Diiodothyronine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:02:41.065080Z","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":[]}