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

Abstract

Progress in studying the androgen receptor (AR), the primary drug target in prostate cancer, has been hampered by challenges in expressing and purifying active multidomain AR for use in cell-free biochemical reconstitution assays. Here we successfully express full-length and truncated AR variants and demonstrate that the oncogenic ETS protein ERG, responsible for half of all prostate cancers, enhances the ability of AR to bind DNA through direct interaction with AR. In addition to providing a biochemical system to evaluate AR activity on different DNA templates, our findings provide insight into why ERG-positive prostate cancers have an expanded AR cistrome.

Document Details

Document Type
Pub Defense Publication
Publication Date
Mar 27, 2020
Source ID
10.1073/pnas.1922159117

Entities

People

  • Albert Antar
  • Charles Sawyers
  • Elizabeth A. Hoover
  • Elizabeth V Wasmuth
  • Sebastian Klinge
  • Yu Chen

Organizations

  • Howard Hughes Medical Institute
  • Memorial Sloan Kettering Cancer Center
  • National Cancer Institute
  • The Rockefeller University
  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Prostate Cancer Biology.