An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1
Howard Hughes Medical Institute · Massachusetts Institute of Technology · +3 more institutions
Abstract
The mammalian target of rapamycin (mTOR) kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin. Surprisingly, these effects are independent of mTORC2 inhibition and are instead because of suppression of rapamycin-resistant functions of mTORC1 that are necessary for cap-dependent…
Citation impact
- FWCI
- 56.13
- Percentile
- 100%
- References
- 47
Authors
10- CCCarson C. Thoreen
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research
- SASeong A. Kang
Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology
- JWJae Won Chang
Dana-Farber Cancer Institute, Harvard University
- QLQingsong Liu
Dana-Farber Cancer Institute, Harvard University
- JZJianming Zhang
Harvard University, Dana-Farber Cancer Institute
Topics & keywords
- mTORC1
- mTORC2
- PI3K/AKT/mTOR pathway
- Mechanistic target of rapamycin
- Cell biology
- Cell growth
- Autophagy
- Biology
- Good health and well-being