Maintenance has been completed and SciCrunch services have been restored. We apologize for any inconvenience it may have caused.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family.

Estrogen acting through the estrogen receptor (ER) is able to regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors. Ligand-activated ER binds DNA and transactivates the promoters of estrogen target genes. In addition, ligand-activated ER can interact with other factors to alter the physiology and growth of cells. Using a yeast two-hybrid screen, we have identified an interaction between ER alpha and the proapoptotic forkhead transcription factor FKHR. The ER alpha-FKHR interaction depends on beta-estradiol and is reduced significantly in the absence of hormone or the presence of Tamoxifen. A glutathione S-transferase pull-down assay was used to confirm the interaction and localized two interaction sites, one in the forkhead domain and a second in the carboxyl terminus. The FKHR interaction was specific to ER alpha and was not detected with other ligand-activated steroid receptors. The related family members, FKHRL1 and AFX, also bound to ER alpha in the presence of beta-estradiol. FKHR augmented ER alpha transactivation through an estrogen response element. Conversely, ER alpha repressed FKHR-mediated transactivation through an insulin response sequence, and cell cycle arrest induced by FKHRL1 in MCF7 cells was abrogated by estradiol. These results suggest a novel mechanism of estrogen action that involves regulation of the proapoptotic forkhead transcription factors.

Pubmed ID: 11435445

Authors

  • Schuur ER
  • Loktev AV
  • Sharma M
  • Sun Z
  • Roth RA
  • Weigel RJ

Journal

The Journal of biological chemistry

Publication Data

September 7, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA070297
  • Agency: NCI NIH HHS, Id: R01 CA070297-06A1
  • Agency: NCI NIH HHS, Id: R01 CA070297-07
  • Agency: NCI NIH HHS, Id: R01 CA070297-08
  • Agency: NCI NIH HHS, Id: R01 CA070297-09
  • Agency: NCI NIH HHS, Id: R01 CA070297-10
  • Agency: NCI NIH HHS, Id: R01 CA070297-11A2
  • Agency: NCI NIH HHS, Id: R01 CA070297-12
  • Agency: NCI NIH HHS, Id: R01 CA087767
  • Agency: NCI NIH HHS, Id: R01 CA087767-01A2
  • Agency: NCI NIH HHS, Id: R01 CA087767-02
  • Agency: NCI NIH HHS, Id: R01 CA087767-03
  • Agency: NCI NIH HHS, Id: R01 CA087767-04
  • Agency: NCI NIH HHS, Id: R01 CA087767-05
  • Agency: NCI NIH HHS, Id: R01 CA77350
  • Agency: NIDDK NIH HHS, Id: R01 DK061002
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-01A1
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-02
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-03
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-04
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-05
  • Agency: NCI NIH HHS, Id: R29 CA070297
  • Agency: NCI NIH HHS, Id: R29 CA070297-03
  • Agency: NCI NIH HHS, Id: R29 CA070297-05
  • Agency: NCI NIH HHS, Id: R29 CA070297-05S1
  • Agency: NIDDK NIH HHS, Id: R56 DK061002
  • Agency: NIDDK NIH HHS, Id: R56 DK061002-06A1

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Binding Sites
  • COS Cells
  • Cell Cycle
  • Cell Nucleus
  • DNA
  • DNA, Complementary
  • Estradiol
  • Estrogen Receptor alpha
  • Estrogens
  • Forkhead Transcription Factors
  • Genes, Reporter
  • Glutathione Transferase
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Nuclear Proteins
  • Plasmids
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Estrogen
  • Repressor Proteins
  • Tamoxifen
  • Transcription Factors
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques