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Updated: Jul 16, 2026
09:07
Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Ligand binding to the androgen receptor induces conformational changes that regulate phosphatase interactions
Chun-Song Yang1, Hong-Wu Xin, Joshua B Kelley
1Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
Molecular and Cellular Biology
|February 28, 2007
Summary
Protein phosphatase 2A (PP2A) targets the androgen receptor (AR) via structural changes induced by Simian virus 40 (SV40) small t antigen (ST). This interaction influences AR conformation and phosphorylation, impacting prostate cancer cell activation.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Cancer Research
Background:
- Protein phosphatase 2A (PP2A) regulates numerous cellular processes.
- The androgen receptor (AR) is a key regulator in prostate cancer.
- Kinase and phosphatase interactions with AR are critical for its function.
Purpose of the Study:
- To elucidate the mechanism of PP2A targeting to the AR.
- To understand how Simian virus 40 (SV40) small t antigen (ST) affects PP2A-AR interactions.
- To investigate the role of these interactions in AR conformation and activation.
Main Methods:
- Studied structural changes in PP2A's A subunit induced by SV40 ST.
- Analyzed AR conformations in response to androgens and antagonists.
- Investigated AR phosphorylation and dephosphorylation in prostate cancer cells.
Main Results:
- SV40 ST binding to PP2A A subunit induces conformational changes enabling discrimination of AR states.
- An AR mutant (T877A) in prostate cancer cells is activated by various ligands without adopting a canonical androgen-induced conformation.
- Androgen binding correlates with increased AR AF-1 phosphorylation, suggesting regulation of kinase access or phosphatase resistance.
Conclusions:
- PP2A targeting to AR is modulated by structural changes in PP2A, influenced by SV40 ST.
- Androgens may enhance AR phosphorylation by inhibiting phosphatase binding or promoting phosphatase-resistant conformations.
- SV40 ST hijacks this mechanism to induce AR dephosphorylation, affecting AR signaling.
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