MTOR
mTOR (mechanistic target of rapamycin) is a kinase that integrates growth factors, nutrients, energy state, and stress into a single decision about whether the cell should build biomass.
Function
mTOR functions in two multiprotein complexes. mTORC1 (with RAPTOR) responds to amino acids, growth factors (through the PI3K–AKT route), and high energy charge; it phosphorylates S6K and 4E-BP1, which drives ribosome biogenesis and cap-dependent translation — the cell’s protein-synthesis program. mTORC2 (with RICTOR) phosphorylates AKT on Ser473 and controls cytoskeletal organization. Rapamycin binds FKBP12 and inhibits mTORC1 allosterically, the mechanism behind the drug’s immunosuppressive and lifespan-extending effects.
In cancer
The pathway is hyperactivated in most human cancers, through PTEN loss, PI3K or AKT mutation, or mTOR itself. Tumors use mTORC1 to keep protein synthesis running under poor conditions, and rapalogs (everolimus, temsirolimus) are approved in renal cell carcinoma and breast cancer. In gerontology, mTORC1 inhibition extends lifespan in mice — the most reproducible pharmacological longevity result in the field — and connects growth-control signaling to the IGF-1 aging axis.
Notes
- Human gene symbol: MTOR; UniProt P42345; 2,549 amino acids; PI3K-related kinase (PIKK) family.