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mTORC1 directly phosphorylates and regulates human MAF1
Annemieke A Michels1, Aaron M Robitaille, Diane Buczynski-Ruchonnet
1Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Molecular and Cellular Biology
|June 3, 2010
Summary
The mechanistic target of rapamycin complex 1 (mTORC1) directly phosphorylates the MAF1 protein, inhibiting its ability to repress RNA polymerase III transcription. This reveals a key signaling pathway controlling cell growth and gene expression.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- mTORC1 is a key regulator of cell growth tied to nutrient availability.
- RNA polymerase (pol) III activity is crucial for protein synthesis and tightly regulated.
- Deregulation of pol III can lead to cell transformation.
Purpose of the Study:
- To identify direct targets of mTORC1.
- To elucidate the mechanism by which MAF1 represses pol III transcription.
- To understand the role of MAF1 phosphorylation in cellular stress responses.
Main Methods:
- Investigated MAF1 phosphorylation sites.
- Utilized rapamycin and Torin1 to inhibit mTORC1.
- Assessed pol III repression under various conditions.
Main Results:
- Human MAF1 is essential for pol III repression during serum starvation or mTORC1 inhibition.
- mTORC1 directly phosphorylates MAF1 on specific residues (S60, S68, S75).
- This phosphorylation event inhibits MAF1's repressor function on pol III transcription.
Conclusions:
- mTORC1 directly phosphorylates MAF1, modulating its activity.
- This represents a novel signaling branch downstream of mTORC1.
- Discovered a molecular mechanism linking mTORC1 signaling to RNA polymerase III regulation.
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