4E-BP1 (eIF4E-binding protein 1)
4E-BP1 normally binds and sequesters eIF4E, blocking cap-dependent translation initiation. Active mTORC1 phosphorylates 4E-BP1 at multiple sites, causing it to release eIF4E and pe...
Classification
Category: Downstream effector / translation-initiation regulator
Aliases: EIF4EBP1, PHAS-I
Relationship to mTOR complexes: Direct mTORC1 substrate; downstream of mTORC1 — see mTORC1 vs mTORC2 for the full complex-level map.
Summary
4E-BP1 normally binds and sequesters eIF4E, blocking cap-dependent translation initiation. Active mTORC1 phosphorylates 4E-BP1 at multiple sites, causing it to release eIF4E and permitting cap-dependent mRNA translation to proceed -- a second, S6K1-independent route by which mTORC1 promotes protein synthesis.
| Upstream of | none recorded |
| Downstream of | MTORC1 |
- mTORC1 directly phosphorylates 4E-BP1 at multiple sites when mTORC1 is active
- Phosphorylated 4E-BP1 releases eIF4E, permitting cap-dependent translation initiation and increased protein synthesis
- 4E-BP1 and S6K1 are the two principal mTORC1 outputs driving protein synthesis in this dataset's pathway map, acting through distinct molecular routes (cap-dependent translation initiation vs. ribosomal/translation-machinery phosphorylation, respectively).
- Rapamycin and rapalogs (see /rapamycin, /sirolimus, /everolimus, /rtb101) inhibit mTORC1 output toward both S6K1 and 4E-BP1, though sensitivity of the two substrates to rapamycin can differ by tissue/context in the broader literature.
Source tier
Tier 2 · Biological synthesis (author-cluster reviews, not primary trial data) Reference synthesis attributed in the brief to the Saxton & Sabatini; Laplante & Sabatini; and Liu & Sabatini mTOR review literature (author-cluster attribution, tier 2, brief ยง4). Exact article-level PMID/DOI not supplied in the sourcing brief and is not fabricated here.