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Updated: Sep 15, 2025
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Published on: May 9, 2020
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Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability
Sofía Cabezudo1, Natalia Cuervo1, Carmen García-Martín1
1Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
FEBS Open Bio
|July 14, 2025
Summary
The WAC protein forms a dynamic complex with mTOR and TELO2, regulating mTORC1 activity based on nutrient availability. This interaction is crucial for cellular responses to glucose and glutamine levels.
Area of Science:
- Cellular Biology
- Molecular Mechanisms
- Protein Interactions
Background:
- The TELO2-TTI1-TTI2 (TTT) and R2TP complexes are chaperones that assist in assembling PIKK kinases, including mTORC1.
- WAC protein is a known regulator of mTORC1, influenced by nutrient availability, and works with R2TP and TTT.
Purpose of the Study:
- To define the molecular interactions of WAC with R2TP and TTT.
- To understand the role of these interactions in mTORC1 regulation under varying nutrient conditions.
Main Methods:
- Purified protein interaction assays.
- Cellular complex analysis under nutrient deprivation and refeeding.
- Transcriptomic and proteomic analysis.
Main Results:
- WAC directly binds mTOR-mLST8, R2TP, and TELO2, but not TTI1 or TTI2.
- WAC forms dynamic complexes with mTOR and TELO2, which associate strongly under nutrient deprivation and dissociate upon refeeding.
- These dynamic interactions correlate with mTORC1 activity changes.
Conclusions:
- WAC forms a regulated complex with mTOR and TELO2, contributing to mTORC1 control in response to glucose and glutamine.
- WAC, mTOR, R2TP, and TTT are co-expressed in human cancers, suggesting a role in cancer biology.
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