Department of Pharmacology and Molecular Toxicology
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 https://www.asbmb.org/journals-news/editorial-policies.
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
The Journal of biological chemistry
Li H, Chen JD. (1998). The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation. Open Access Publications by UMMS Authors. https://doi.org/10.1074/jbc.273.10.5948. Retrieved from https://escholarship.umassmed.edu/oapubs/781