Related Experiment Video

Updated: Dec 25, 2025

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

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Modulation of androgen receptor DNA binding activity through direct interaction with the ETS transcription factor ERG

Elizabeth V Wasmuth1, Elizabeth A Hoover1, Albert Antar2

  • 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.

Proceedings of the National Academy of Sciences of the United States of America
|March 30, 2020
PubMed

Insights

Androgen receptor (AR) reprogramming in prostate cancer involves ERG cofactor interaction. This biochemical insight explains how ETS fusions alter AR DNA binding, impacting cancer progression.

Area of Science:

  • Molecular biology
  • Cancer research
  • Biochemistry

Background:

  • The androgen receptor (AR) is a key target in prostate cancer.
  • AR's role in prostate luminal epithelium survival is crucial.
  • AR cistrome reprogramming occurs in prostate cancer, especially with ETS fusions, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the molecular basis of AR cistrome reprogramming in prostate cancer.
  • To investigate the role of ERG as a cofactor in AR DNA binding.
  • To understand the biochemical interactions driving AR dysregulation in ETS-driven prostate cancers.

Main Methods:

  • Utilized a minimal cell-free system with purified proteins.
  • Investigated interdomain cooperativity within the AR.
  • Identified and characterized the AR-interacting motif (AIM) in the ERG ETS domain.

Main Results:

  • Demonstrated AR interdomain cooperativity and N-terminal autoinhibition.
  • Identified ERG as an AR cofactor that enhances DNA binding.
  • ERG interacts with AR via a novel AIM in the ETS domain, independent of ERG's DNA binding.
  • This interaction is conserved across ETS factors implicated in prostate cancer.

Conclusions:

  • Biochemical insights into AR-mediated transcriptional regulation in prostate cancer.
  • ERG acts as a critical cofactor, reprogramming the AR cistrome.
  • Understanding this interaction mechanism is vital for targeted prostate cancer therapies.
Keywords:
antiandrogencistromeprostate cancer

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