Title

RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2

UMMS Affiliation

Department of Pharmacology and Molecular Toxicology

Publication Date

8-5-1997

Document Type

Article

Subjects

Amino Acid Sequence; Animals; Cell Line; Cloning, Molecular; Histone Acetyltransferases; Humans; Infant; Molecular Sequence Data; Nuclear Receptor Coactivator 2; Receptors, Steroid; Sequence Alignment; Sequence Analysis; Trans-Activators; Transcription Factors; Transfection

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Steroids, thyroid hormones, vitamin D3, and retinoids are lipophilic small molecules that regulate diverse biological effects such as cell differentiation, development, and homeostasis. The actions of these hormones are mediated by steroid/nuclear receptors which function as ligand-dependent transcriptional regulators. Transcriptional activation by ligand-bound receptors is a complex process requiring dissociation and recruitment of several additional cofactors. We report here the cloning and characterization of receptor-associated coactivator 3 (RAC3), a human transcriptional coactivator for steroid/nuclear receptors. RAC3 interacts with several liganded receptors through a mechanism which requires their respective ligand-dependent activation domains. RAC3 can activate transcription when tethered to a heterologous DNA-binding domain. Overexpression of RAC3 enhances the ligand-dependent transcriptional activation by the receptors in mammalian cells. Sequence analysis reveals that RAC3 is related to steroid receptor coactivator 1 (SRC-1) and transcriptional intermediate factor 2 (TIF2), two of the most potent coactivators for steroid/nuclear receptors. Thus, RAC3 is a member of a growing coactivator network that should be useful as a tool for understanding hormone action and as a target for developing new therapeutic agents that can block hormone-dependent neoplasia.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8479-84.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

9238002