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Updated: Jul 16, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Yeast-based screening to identify modulators of G-protein signaling using uncontrolled cell division cycle by
Kyung-Sook Chung1, Misun Won, Jung-Joon Lee
1Biopharmaceutical Division, KRIBB, Daejeon 305-806, Republic of Korea.
Abstract:
Stm1, a G-protein coupled receptor, which senses nutritional state drives cells to stop the proliferative cell cycle and enter meiosis under nutritionally deficient conditions in Schizosaccharomyces pombe. It was shown that overexpression of Stm1 led growth inhibition and uncontrolled mitotic haploidization presumably by the premature initiation of mitosis. Sty1 and Gpa2 seem to play important roles for Stm1 to deliver starvation signal to induce downstream function. Based on the observation that conversion of diploid to haploid by overexpression of Stm1 can be easily detected as pink or red colonies in the media containing low adenine, HTS drug screening system to identify modulators of GPCR was established and tested using 413 compounds. Four very potent modulators of GPCR including Biochanin A, which possess strong inhibitory activity against uncontrolled cell division, were identified in this screening. This study provides the yeast-based platform that allows robust cellular assays to identify novel modulators of G-protein signaling and MAP kinase pathway.
Insights
Stm1, a G-protein coupled receptor, halts cell division and induces meiosis during nutrient scarcity in yeast. A high-throughput screening system identified potent modulators of this pathway, including Biochanin A, which inhibits uncontrolled cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Yeast Genetics
Background:
- Stm1, a G-protein coupled receptor (GPCR), regulates cell cycle progression in response to nutritional status in Schizosaccharomyces pombe.
- Overexpression of Stm1 can lead to growth inhibition and mitotic haploidization, suggesting a role in premature cell cycle initiation.
Purpose of the Study:
- To establish a high-throughput screening (HTS) system for identifying modulators of GPCR signaling using Stm1.
- To identify novel compounds that regulate Stm1-mediated cell cycle control and starvation response.
Main Methods:
- Development of an HTS drug screening system based on Stm1-induced haploidization, visualized by colony color in low adenine media.
- Screening of 413 diverse compounds to identify modulators of GPCR activity.
- Assay validation using identified potent modulators.
Main Results:
- A robust yeast-based HTS platform was established for GPCR modulator discovery.
- Four potent GPCR modulators were identified from the 413-compound screen.
- Biochanin A was identified as a potent inhibitor of uncontrolled cell division.
Conclusions:
- The study presents a valuable yeast model for discovering novel modulators of G-protein signaling and the MAP kinase pathway.
- The identified compounds, particularly Biochanin A, offer potential therapeutic leads for conditions involving aberrant cell proliferation.
- This platform facilitates the study of nutrient sensing pathways and their impact on cell cycle regulation.
