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A negative coregulator for the human ER.

Publication ,  Journal Article
Norris, JD; Fan, D; Sherk, A; McDonnell, DP
Published in: Mol Endocrinol
March 2002

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.

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Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

March 2002

Volume

16

Issue

3

Start / End Page

459 / 468

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Tissue Distribution
  • Tamoxifen
  • Repressor Proteins
  • Receptors, Estrogen
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • RNA
 

Citation

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Norris, J. D., Fan, D., Sherk, A., & McDonnell, D. P. (2002). A negative coregulator for the human ER. Mol Endocrinol, 16(3), 459–468. https://doi.org/10.1210/mend.16.3.0787
Norris, John D., Daju Fan, Andrea Sherk, and Donald P. McDonnell. “A negative coregulator for the human ER.Mol Endocrinol 16, no. 3 (March 2002): 459–68. https://doi.org/10.1210/mend.16.3.0787.
Norris JD, Fan D, Sherk A, McDonnell DP. A negative coregulator for the human ER. Mol Endocrinol. 2002 Mar;16(3):459–68.
Norris, John D., et al. “A negative coregulator for the human ER.Mol Endocrinol, vol. 16, no. 3, Mar. 2002, pp. 459–68. Pubmed, doi:10.1210/mend.16.3.0787.
Norris JD, Fan D, Sherk A, McDonnell DP. A negative coregulator for the human ER. Mol Endocrinol. 2002 Mar;16(3):459–468.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

March 2002

Volume

16

Issue

3

Start / End Page

459 / 468

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Tissue Distribution
  • Tamoxifen
  • Repressor Proteins
  • Receptors, Estrogen
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • RNA