SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity.


Journal Article

The ability of steroid receptor RNA activator (SRA), an AF-1 coactivator, to contribute to differences in estrogen receptor (ER)-alpha and ERbeta transcriptional activity was tested. In transient transfections, SRA expression increased ERalpha- and ERbeta-dependent gene expression. However, when the receptors' amino-terminal A/B regions were examined as GAL4 DNA binding domain fusions, SRA enhanced the activity of GAL-ABalpha but not GAL-ABbeta. Exogenous SRA also enhanced AF-2 activity for both receptors, indicating that SRA effects are not limited to AF-1. Simultaneously mutating three phosphorylation sites within GAL-ABalpha domain only modestly reduced SRA coactivation of GAL-ABalpha, suggesting that phosphorylation does not play a major role in SRA function relative to this domain. SRA enhanced ERalpha activity stimulated by 4-hydroxytamoxifen, but was unable to convert this mixed antiestrogen to an ERbeta agonist. Thus, SRA is an ERalpha AF-1-specific coactivator that enhances the agonist activity of tamoxifen-bound ERalpha and may contribute to tamoxifen resistance.

Full Text

Duke Authors

Cited Authors

  • Coleman, KM; Lam, V; Jaber, BM; Lanz, RB; Smith, CL

Published Date

  • October 8, 2004

Published In

Volume / Issue

  • 323 / 1

Start / End Page

  • 332 - 338

PubMed ID

  • 15351741

Pubmed Central ID

  • 15351741

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2004.08.090


  • eng

Conference Location

  • United States