title: Liganded RARalpha and RARgamma interact with but are repressed by TNIP1.
abstract: Nuclear receptor (NR) transcriptional activity is controlled by agonist binding and concomitant exchange of receptor-associating corepressor proteins for NR box-containing, receptor AF-2-targeting coactivator proteins. We report here that TNIP1 is an atypical NR coregulator. Requirements for TNIP1-RAR interaction-its NR boxes, ligand, and the receptor's AF-2 domain-are characteristic of coactivators. However, TNIP1 reduces RAR activity. Repression is partially relieved by SRC1, suggesting interference with coactivator recruitment as a mechanism of TNIP1 repression. TNIP1 does not bind RXRalpha and RARalpha AF-2 domain, necessary for that receptor's association with TNIP1, is insufficient to confer upon RXRalpha interaction with TNIP1. Preferential interaction of RARalpha over RARgamma with TNIP1 can be mapped to RARalpha ligand binding domain helices 5-9 and suggests regions outside the receptor helix 12 modulate interaction of NRs and NR box-containing corepressors. TNIP1 repression of RARs in the presence of RA places it in a small category of corepressors of agonist-bound NRs.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Gurevich
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Aneskievich
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009687:Nuclear Proteins / Q000378:metabolism; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma
chemical_list: D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D008024:Ligands; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C117046:TNIP1 protein, human