Anne-Claude Gingras
Showed in 1999 that mTOR phosphorylates 4E-BP1 in a priming two-step mechanism, and now leads work on interaction proteomics (including BioID) that maps how cells read signals such as mTORC1
Senior Investigator & Director, Lunenfeld-Tanenbaum Research Institute · Vice President, Research, Sinai Health · Professor, University of Toronto
Portrait: Lunenfeld-Tanenbaum Research Institute, Sinai Health
Anne-Claude Gingras did the work in GIN1999 at McGill University in Nahum Sonenberg's field, which studies how cells start making proteins. The protein 4E-BP1 holds back the factor eIF4E; when 4E-BP1 is phosphorylated it lets go, and protein synthesis speeds up. The paper asked which sites mTOR itself phosphorylates and in what order.
The answer was a two-step mechanism. mTOR first adds phosphate to two sites, Thr-37 and Thr-46, and this acts as a priming event that is needed before the later, serum-sensitive sites can be phosphorylated. It was an early, concrete picture of how mTOR turns a growth signal into more translation.
Today she is Senior Investigator and Director of the Lunenfeld-Tanenbaum Research Institute in Toronto and Vice President, Research, at Sinai Health. Her laboratory develops mass spectrometry and proximity-labelling methods to map protein interactions and locations, and studies signalling pathways including mTORC1, relevant to cancer, neurodegeneration and rare diseases. She holds a Canada Research Chair in Functional Proteomics.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 1999 | M | Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism GIN1999 First author: mTOR phosphorylates 4E-BP1 at Thr-37 and Thr-46 as a priming step required for later phosphorylation sites that release eIF4E. |
| 2002 | M | A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus TAN2002 Co-author: mTOR, 4E-BP1, 4E-BP2 and eIF4E sit in hippocampal dendrites near synapses, and rapamycin reduced late-phase LTP in rodent hippocampal slices. |
Co-authors in the Atlas
People with a profile here who share at least one study with Anne-Claude Gingras.
- Nahum Sonenberg 2 shared studies Co-discovered the mRNA cap-binding protein eIF4E and the 4E-BP proteins that restrain it, and showed how mTOR releases this brake to control protein synthesis
- Erin M. Schuman Studies how neurons make and break down proteins locally in dendrites and axons; her group helped tie a rapamycin-sensitive mTOR pathway to the protein-synthesis-dependent phase of synaptic plasticity.
- Robert T. Abraham Co-discovered the mammalian target of rapamycin in 1995, giving it the name mTOR, and showed that it directly phosphorylates the translation repressor 4E-BP1 (PHAS-I)
- Shao-Jun Tang Neuroscientist who, as a postdoc in Erin Schuman's group at Caltech, helped show that a rapamycin-sensitive mTOR pathway is needed for the protein-synthesis-dependent late phase of hippocampal LTP; his lab now studies chronic pain.
- Steven P. Gygi Mass-spectrometry scientist whose Harvard lab builds large-scale proteomics methods, including the BioPlex human protein-interaction map, and contributed proteomics to the discoveries of the CASTOR and SAMTOR nutrient sensors
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