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A sweet way to regulate cellular growth: OGT and mTOR join forces
Pedro Latorre-Muro1, Pere Puigserver1
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Molecular Cell
|August 18, 2023
Summary
Researchers discovered how glucose levels activate mTORC1, a key cell growth regulator. The enzyme OGT links glucose to mTORC1 activation, promoting cell proliferation.
Area of Science:
- Cell Biology
- Metabolism
- Molecular Signaling
Background:
- The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and proliferation.
- Dysregulation of mTORC1 signaling is implicated in various diseases, including cancer and metabolic disorders.
- Understanding how mTORC1 is regulated by nutrient availability, particularly glucose, is crucial for deciphering cellular responses.
Purpose of the Study:
- To elucidate the mechanism by which glucose sensing regulates mTORC1.
- To identify the key enzymes and proteins involved in this glucose-sensing pathway.
- To understand how this pathway influences cellular processes like proliferation.
Main Methods:
- Investigated the role of the glycosyltransferase O-GlcNAc transferase (OGT) in mTORC1 activation.
- Utilized biochemical assays and cell-based experiments to study protein interactions and signaling.
- Examined the effects of OGT-mediated mTORC1 activation on lysosomal targeting and cell proliferation.
Main Results:
- Demonstrated that OGT directly senses glucose levels.
- Showed that OGT activates mTORC1 by modifying Raptor, a key mTORC1 component.
- Confirmed that activated mTORC1 is targeted to lysosomes, promoting cell proliferation.
Conclusions:
- OGT acts as a glucose sensor that links glucose availability to mTORC1 activation.
- This glucose-sensing mechanism involves OGT-mediated Raptor modification and lysosomal targeting of mTORC1.
- The findings reveal a novel pathway regulating cell proliferation in response to glucose, with implications for metabolic diseases.
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