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Updated: Aug 5, 2026
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A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
The 14-3-3 proteins positively regulate rapamycin-sensitive signaling
P G Bertram1, C Zeng, J Thorson
1Department of Pathology Washington University School of Medicine St. Louis, Missouri, 63110, USA.
Current Biology : CB
|November 21, 1998
Summary
Researchers identified 14-3-3 proteins as key players in Tor signaling, a pathway targeted by the immunosuppressant rapamycin. Understanding 14-3-3 protein function is crucial for rapamycin-sensitive signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The kinase Tor is a critical regulator of cell cycle progression and a target of the immunosuppressive drug rapamycin.
- The precise molecular mechanisms underlying Tor signaling pathways remain largely unknown.
Purpose of the Study:
- To investigate the role of 14-3-3 proteins in rapamycin-sensitive signaling pathways.
- To elucidate the structural and functional aspects of 14-3-3 proteins in yeast.
Main Methods:
- Isolation of Saccharomyces cerevisiae genes BMH1 and BMH2 as multicopy suppressors of rapamycin-induced growth inhibition.
- Analysis of the effects of BMH gene deletions and mutations in the 14-3-3 phosphopeptide-binding pocket on rapamycin sensitivity.
Main Results:
- BMH1 and BMH2, encoding 14-3-3 homologs, were identified as suppressors of rapamycin's growth-inhibitory effects.
- Gene dosage of BMH genes influenced hypersensitivity to rapamycin.
- Mutations affecting phosphoserine-binding abolished rapamycin resistance, while substitutions near these sites conferred dominant resistance.
Conclusions:
- 14-3-3 proteins are integral components of rapamycin-sensitive signaling pathways.
- The study provides novel insights into the structure-function relationships of 14-3-3 proteins, particularly their role in phosphopeptide binding and signaling modulation.
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