Pathway link MTORC1-4EBP1
mTORC1 4E-BP1
mTORC1 inhibits 4E-BP1.
mTORC1 tags 4E-BP1 so it lets go of another protein, freeing up protein-building – but the standard drug (rapamycin) only partly blocks this step.
The conditions it holds under
Cell and in vitro evidence (human and mouse cells, with C. elegans RNAi in one study). Rapamycin blocks this phosphorylation only partly, and individual sites differ in how sensitive they are (KAN2013). Not shown in people by these studies.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- mammalian cells
- Where in the cell
- cytosol
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 1998 | M | RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1BUR1998 RAFT1/mTOR directly phosphorylates p70 S6K (Thr389) and 4E-BP1, the two central translational effectors. |
| 2002 | M | Raptor, a binding partner of target of rapamycin (TOR), mediates TOR actionHARA2002 Independent co-discovery of Raptor (same issue of Cell as Kim 2002). Showed Raptor is essential for mTOR to phosphorylate 4E-BP1 and S6K1, and that knocking it down in worms mimics loss of TOR - confirming Raptor as a core, conserved mediator of TOR action. |
| 2009 | M | Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2FEL2009 The parallel discovery to Thoreen 2009 (same year), from the Shokat lab. Their TORKinibs (PP242, PP30) block mTOR's active site, hitting both complexes and shutting down cap-dependent translation that rapamycin misses. Together these two papers established a whole new drug class beyond rapamycin. |
| 1999 | M | Regulation of 4E-BP1 phosphorylation: a novel two-step mechanismGIN1999 4E-BP1 is phosphorylated by an ordered, priming two-step mechanism that controls its release of eIF4E. |
| 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. |
| 1998 | M | Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanismHAR1998 Amino acid sufficiency signals through mTOR to p70 S6K and 4E-BP1 via a common effector, first linking nutrients to mTOR. |
| 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. |
| 2003 | M | The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motifNOJ2003 Raptor binds mTOR substrates via their TOS motifs, acting as the substrate-presenting scaffold of mTORC1. |
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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