UMMS Affiliation

Department of Pharmacology and Molecular Toxicology

Publication Date


Document Type



Animals; CREB-Binding Protein; Cell Line; Cercopithecus aethiops; Histone Acetyltransferases; Nuclear Proteins; Peptide Fragments; RNA, Messenger; Receptors, Steroid; Retinoids; Trans-Activation (Genetics); Trans-Activators; Transcription Factors; Transfection


Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology


Transcriptional 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.


transcriptional coactivators, nuclear hormone receptors, receptor-associated coactivator 3, RAC3, nuclear receptor coactivators

Rights and Permissions

© 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

DOI of Published Version



This research was originally published in: J Biol Chem. 1998 Mar 6;273(10):5948-54. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID