Coactivators for the orphan nuclear receptor RORα Journal Article
| Authors: | Atkins, G. B.; Hu, X.; Guenther, M. G.; Rachez, C.; Freedman, L. P.; Lazar, M. A. |
| Article Title: | Coactivators for the orphan nuclear receptor RORα |
| Abstract: | A mutation in the nuclear orphan receptor RORα results in a severe impairment of cerebellar development by unknown mechanisms. We have shown previously that RORα contains a strong constitutive activation domain in its C terminus. We therefore searched for mammalian RORα coactivators using the minimal activation domain as bait in a two-hybrid screen. Several known and putative coactivators were isolated, including glucocorticoid receptor-interacting protein-1 (GRIP-1) and peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP/TRAP220/DRIP205). These interactions were confirmed in vitro and require the intact activation domain of RORα although different requirements for interaction with GRIP-1 and PBP were detected. Even in the absence of exogenous ligand, RORα interacts with a complex or complexes of endogenous proteins, similar to those that bind to ligand-occupied thyroid hormone and vitamin D receptors. Both PBP and GRIP-1 were shown to be present in these complexes. Thus we have identified several potential RORα coactivators that, in contrast to the interactions with hormone receptors, interact with RORα in yeast, in bacterial extracts, and in mammalian cells in vivo and in vitro in the absence of exogenous ligand. GRIP-1 functioned as a coactivator for the RORα both in yeast and in mammalian cells. Thus, GRIP-1 is the first proven coactivator for RORα. |
| Keywords: | human cell; mutation; mammalia; animals; mice; carboxy terminal sequence; cell line; protein binding; bacteria (microorganisms); transcription factors; gene expression regulation; saccharomyces cerevisiae; carrier proteins; adaptor proteins, signal transducing; binding protein; binding sites; trans-activators; cell nucleus receptor; vitamin d receptor; thyroid hormone; cell extracts; nuclear receptor coactivator 2; glucocorticoid receptor; receptors, cytoplasmic and nuclear; cell-free system; humans; human; priority journal; article; peroxisome proliferator activated receptor |
| Journal Title: | Molecular Endocrinology |
| Volume: | 13 |
| Issue: | 9 |
| ISSN: | 0888-8809 |
| Publisher: | Endocrine Society |
| Date Published: | 1999-01-01 |
| Start Page: | 1550 |
| End Page: | 1557 |
| Language: | English |
| PUBMED: | 10478845 |
| PROVIDER: | scopus |
| DOI: | 10.1210/mend.13.9.0343 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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