title: Jab1 is a T2-dependent coactivator or a T3-dependent corepressor of TRB1-mediated gene regulation.
abstract: 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-T2(T2). We found that jun activation domain-binding protein1 (Jab1) interacts with L-Trb1 + T2complex. 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 T2is bound to L-Trb1 or hTRB1, Jab1 acts as a coactivator of transcription, whereas it has corepressor activity when interacting with the T3-bound S-Trb1 or hTRB1. These mechanisms could explain some of the pleiotropic actions exerted by THs to regulate diverse biological processes.
authors.affiliation: Departamento de Neurobiología Celular y MolecularInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hernández-Puga
authors.affiliation: Departamento de Neurobiología Celular y MolecularInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Mendoza
authors.affiliation: Programa de Investigación de Cáncer de Mama y Departamento de Biología Molecular y BiotecnologíaInstituto de Investigaciones Biomédicas, UNAM, México, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: León-Del-Río
authors.affiliation: Departamento de Neurobiología Celular y MolecularInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico aureao@unam.mx.
authors.forename: Aurea
authors.initials: A
authors.lastname: Orozco
mesh_terms: D000818:Animals; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology*
chemical_list: C490121:Gps1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D000075686:COP9 Signalosome Complex
keywords: 3, 5-diiodothyronine; Jab1; coregulator; nuclear receptor; thyroid hormone receptor