Pathway link RAPA-MTORC1
Rapamycin mTORC1
Rapamycin inhibits mTORC1.
Rapamycin, carried by its helper protein FKBP12, jams part of mTORC1 – it blocks some of what mTORC1 does but not all of it.
The conditions it holds under
Directness is graded indirect because the mechanism requires FKBP12, as for everolimus and the bi-sterics. Acute effect only; the chronic effect on mTORC2 is the separate RAPA-MTORC2 edge.
- Time it takes
- minutes
- Step
- indirect (through steps not drawn here)
- Measured in
- human cells
- Where in the cell
- lysosome
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 1992 | M | Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinasesCHU1992 Rapamycin-FKBP12 complex blocks growth-factor activation of p70 S6 kinase, linking the drug to a specific mitogenic pathway. |
| 1994 | M | A mammalian protein targeted by G1-arresting rapamycin-receptor complexBRO1994 Purified FRAP (mTOR) as the mammalian FKBP12-rapamycin target homologous to yeast TOR1/2. |
| 1994 | M | RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORsSAB1994 Discovery of the protein RAFT1 (today's mTOR) as the direct target of the FKBP12-rapamycin complex; one of three 1994 reports (with Brown et al. and Chiu et al.) that identified mammalian TOR, three years after TOR was found in yeast. |
| 1995 | M | Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cellsSAB1995 Isolated mTOR as the FKBP12-rapamycin-associated protein controlling G1-S progression. |
| 1996 | M | Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAPCHO1996 The crystal structure that showed HOW rapamycin works at the atomic level: one rapamycin molecule glues two proteins together - FKBP12 and mTOR's FRB domain - by plugging into two hydrophobic pockets at once. A textbook example of a small molecule acting as 'molecular glue' to force protein dimerization. |
| 2008 | A | Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and functionMEI2008 mTOR inhibition rescues a neuronal tuberous-sclerosis model, supporting rapamycin for TSC neurology. |
| 2013 | M | mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycinKAN2013 Each mTORC1 phosphorylation site has its own intrinsic 'substrate quality'. Good substrates stay phosphorylated when mTORC1 is partly inhibited by rapamycin or starvation, poor ones drop out first, and changing a few residues around a site shifts its sensitivity in cells. One level of mTORC1 activity can therefore produce different output profiles. |
| 2002 | M | Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4EFIN2002 mTOR controls mammalian cell size through its downstream translational targets S6K1 and 4E-BP1/eIF4E. |
| 1997 | M | Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycinBRU1997 mTOR directly phosphorylates 4E-BP1 (PHAS-I), releasing eIF4E and establishing mTOR's role in translational control. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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