A negative coregulator for the human ER.

Journal Article

ERalpha is a ligand-activated transcription factor and a key regulator of the processes involved in cellular proliferation and differentiation. In addition, aberrant ERalpha activity is linked to several pathological conditions including breast cancer. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERalpha. We report here the isolation of a protein, denoted RTA for repressor of tamoxifen transcriptional activity, which contains an RNA recognition motif and interacts with the receptor N-terminal activation domain. RTA interacts with RNA in vitro, and its overexpression inhibits the partial agonist activity manifest by the antiestrogen tamoxifen while minimally affecting E2-activated transcription. Mutation of the RNA recognition motif alters RNA binding specificity and results in a dominant negative form of RTA that leads to derepression of ERalpha transcriptional activity, allowing all classes of antiestrogens to manifest partial agonist activity and enhancing agonist efficacy. These findings suggest a role for RNA binding proteins as coregulatory factors of the nuclear receptor family and reveal a novel mechanism by which antiestrogens can manifest agonist activities in some tissues.

Full Text

Duke Authors

Cited Authors

  • Norris, JD; Fan, D; Sherk, A; McDonnell, DP

Published Date

  • March 2002

Published In

Volume / Issue

  • 16 / 3

Start / End Page

  • 459 - 468

PubMed ID

  • 11875103

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/mend.16.3.0787

Language

  • eng

Conference Location

  • United States