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Ligand-specific dynamics of the androgen receptor at its response element in living cells.

Publication ,  Journal Article
Klokk, TI; Kurys, P; Elbi, C; Nagaich, AK; Hendarwanto, A; Slagsvold, T; Chang, C-Y; Hager, GL; Saatcioglu, F
Published in: Mol Cell Biol
March 2007

Androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. Androgens act through the androgen receptor (AR), which is a ligand-modulated transcription factor. Antiandrogens block AR function and are widely used in disease states, but little is known about their mechanism of action in vivo. Here, we describe a rapid differential interaction of AR with target genomic sites in living cells in the presence of agonists which coincides with the recruitment of BRM ATPase complex and chromatin remodeling, resulting in transcriptional activation. In contrast, the interaction of antagonist-bound or mutant AR with its target was found to be kinetically different: it was dramatically faster, occurred without chromatin remodeling, and resulted in the lack of transcriptional inhibition. Fluorescent resonance energy transfer analysis of wild-type AR and a transcriptionally compromised mutant at the hormone response element showed that intramolecular interactions between the N and C termini of AR play a key functional role in vivo compared to intermolecular interactions between two neighboring ARs. These data provide a kinetic and mechanistic basis for regulation of gene expression by androgens and antiandrogens in living cells.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 2007

Volume

27

Issue

5

Start / End Page

1823 / 1843

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Tosyl Compounds
  • Testosterone
  • Response Elements
  • Receptors, Androgen
  • Promoter Regions, Genetic
  • Plasmids
  • Nitriles
  • Models, Biological
  • Mifepristone
 

Citation

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Klokk, T. I., Kurys, P., Elbi, C., Nagaich, A. K., Hendarwanto, A., Slagsvold, T., … Saatcioglu, F. (2007). Ligand-specific dynamics of the androgen receptor at its response element in living cells. Mol Cell Biol, 27(5), 1823–1843. https://doi.org/10.1128/MCB.01297-06
Klokk, Tove I., Piotr Kurys, Cem Elbi, Akhilesh K. Nagaich, Anindya Hendarwanto, Thomas Slagsvold, Ching-Yi Chang, Gordon L. Hager, and Fahri Saatcioglu. “Ligand-specific dynamics of the androgen receptor at its response element in living cells.Mol Cell Biol 27, no. 5 (March 2007): 1823–43. https://doi.org/10.1128/MCB.01297-06.
Klokk TI, Kurys P, Elbi C, Nagaich AK, Hendarwanto A, Slagsvold T, et al. Ligand-specific dynamics of the androgen receptor at its response element in living cells. Mol Cell Biol. 2007 Mar;27(5):1823–43.
Klokk, Tove I., et al. “Ligand-specific dynamics of the androgen receptor at its response element in living cells.Mol Cell Biol, vol. 27, no. 5, Mar. 2007, pp. 1823–43. Pubmed, doi:10.1128/MCB.01297-06.
Klokk TI, Kurys P, Elbi C, Nagaich AK, Hendarwanto A, Slagsvold T, Chang C-Y, Hager GL, Saatcioglu F. Ligand-specific dynamics of the androgen receptor at its response element in living cells. Mol Cell Biol. 2007 Mar;27(5):1823–1843.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 2007

Volume

27

Issue

5

Start / End Page

1823 / 1843

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Tosyl Compounds
  • Testosterone
  • Response Elements
  • Receptors, Androgen
  • Promoter Regions, Genetic
  • Plasmids
  • Nitriles
  • Models, Biological
  • Mifepristone