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Updated: May 2, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 16, 2013

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Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway

Ping Zhu1, Sung Hee Baek, Eliot M Bourk

  • 1Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Cell
|February 14, 2006
PubMed

Insights

Prostate cancer cells and macrophages trigger selective androgen receptor antagonists/modulators (SARMs) to activate gene expression. This switch involves a conserved motif, TAB2, and inflammatory signals, linking reproductive functions to nuclear receptor responses.

Area of Science:

  • Molecular biology
  • Endocrinology
  • Cancer research

Background:

  • Understanding transcriptional regulation is key for development, homeostasis, and hormone-dependent cancers.
  • Selective androgen receptor antagonists/modulators (SARMs) are crucial in managing prostate cancer.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind the switch in SARM function from repression to activation.
  • To investigate the role of prostate cancer cell/macrophage interactions in this functional switch.

Main Methods:

  • Investigated conserved N-terminal L/HX7LL motifs in sex steroid receptors.
  • Studied the recruitment of TAB2 to N-CoR corepressor complexes.
  • Examined the role of inflammatory signals, MEKK1, and N-CoR/HDAC complex dismissal.

Main Results:

  • Discovered that specific prostate cancer cell/macrophage interactions switch SARM function from repression to activation.
  • Identified a conserved L/HX7LL motif mediating TAB2 recruitment to N-CoR.
  • Demonstrated that TAB2 senses inflammatory signals, recruiting MEKK1 to dismiss N-CoR/HDAC, leading to derepression of androgen and estrogen receptor target genes.

Conclusions:

  • A conserved sensor mechanism links inflammatory and nuclear receptor ligand responses.
  • This mechanism reverses sex steroid-dependent repression of target genes in response to inflammation.
  • The findings connect inflammatory signaling pathways with nuclear receptor function in reproductive biology and cancer.

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