The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation
UMass Chan AffiliationsDepartment of Pharmacology and Molecular Toxicology
nuclear hormone receptors
receptor-associated coactivator 3
nuclear receptor coactivators
Cellular and Molecular Physiology
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AbstractTranscriptional coactivators are involved in gene activation by nuclear hormone receptors. The receptor-associated coactivator 3 (RAC3) was recently identified to be highly related to the steroid receptor coactivator-1 and transcriptional intermediate factor 2, thereby establishing a novel family of nuclear receptor coactivators. In this study, we identified a RAC3 fragment containing three LXXLL motifs conserved among this family, which is sufficient to mediate nuclear receptor interaction in vivo and in vitro. Point mutations that disrupt ligand-dependent activation function of the receptor inhibited the interaction. We found that a 162-amino acid fragment of RAC3 conferred transcriptional activation and recruited the CREB-binding protein and that three distinct LXXLL motifs mediated the transcriptional activation. A trimeric far Western analysis demonstrated the formation of a ternary complex containing CREB-binding protein, RAC3, and the receptor. In addition, we showed that RAC3, transcriptional intermediate factor 2, and steroid receptor coactivator-1 are expressed in specific tissues and cancer cells and that RAC3 transcript is directly up-regulated by retinoid treatment. These results suggest that RAC3 may contribute to amplified transcriptional responses through both recruitment of additional coactivators and autoregulation by the receptor-coactivator complex.
This research was originally published in: J Biol Chem. 1998 Mar 6;273(10):5948-54. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42431
Rights© 1998 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at https://www.asbmb.org/journals-news/editorial-policies.
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