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Related Concept Videos

Yeast Signaling01:28

Yeast Signaling

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Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Simulating androgen receptor selection in designer yeast.

Haoran Zhang1,2, Lu Zhang1,2, Yipeng Xu3

  • 1Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, PR China.

Synthetic and Systems Biotechnology
|August 26, 2022
PubMed
Summary

A new yeast assay accurately screens androgen receptor (AR) mutations in prostate cancer (PCa). This tool aids in understanding treatment resistance and developing personalized medicine for PCa patients.

Keywords:
Androgen receptor antagonistsAndrogen receptor mutationsProstate cancerSaccharomyces cerevisiae

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Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Androgen receptor (AR) mutations drive prostate cancer (PCa) and therapy resistance.
  • Next-generation sequencing (NGS) detects AR mutations, but clinical interpretation remains challenging for precision medicine.
  • Understanding AR variant function is crucial for effective PCa treatment strategies.

Purpose of the Study:

  • To develop a novel yeast reporter assay for functional screening of AR mutants.
  • To simulate AR selection under AR antagonist pressure.
  • To provide a tool for interpreting clinical AR variants and guiding precision medicine in PCa.

Main Methods:

  • A designer yeast reporter system was established to assess AR mutant activity.
  • Yeast growth in histidine-free medium served as a readout for AR transactivation.
  • The assay utilized AR antagonists like enzalutamide (ENZ), bicalutamide (BIC), and cyproterone acetate (CPA).

Main Results:

  • The yeast assay successfully identified AR mutants conferring resistance to AR antagonists.
  • The F877L AR mutant, known to resist ENZ, also showed partial resistance to CPA.
  • The assay demonstrated applicability to various AR mutants, including those causing androgen insensitivity syndrome (AIS).

Conclusions:

  • A simple and efficient yeast assay enables precise, one-pot screening of AR mutants.
  • This assay provides valuable functional insights into AR variants relevant to PCa and treatment resistance.
  • The findings offer a reference for developing tailored therapies for prostate cancer patients.