EIF4EBP1

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EIF4EBP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEIF4EBP1, 4E-BP1, 4EBP1, BP-1, PHAS-I, eukaryotic translation initiation factor 4E binding protein 1
External IDsOMIM: 602223; MGI: 103267; HomoloGene: 3021; GeneCards: EIF4EBP1; OMA:EIF4EBP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1978

13685

Ensembl

ENSG00000187840

ENSMUSG00000031490

UniProt

Q13541

Q60876

RefSeq (mRNA)

NM_004095

NM_007918

RefSeq (protein)

NP_004086

NP_031944

Location (UCSC)Chr 8: 38.03 – 38.06 MbChr 8: 27.75 – 27.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Eukaryotic translation initiation factor 4E-binding protein 1 (also known as 4E-BP1) is a protein that in humans is encoded by the EIF4EBP1 gene.[5] It inhibits cap-dependent translation by binding to translation initiation factor eIF4E. Phosphorylation of 4E-BP1 results in its release from eIF4E, thereby allows cap-dependent translation to continue thereby increasing the rate of protein synthesis.[5]

Phosphorylation

Phosphorylated 4E-BP1 is thought to be a marker of upstream signaling (mTOR) activation. 4E-BP1 has seven phospho-sites, the three most important of which are the initiation site Thr 37/Thr 46, the second site Thr 70, and the final site Ser65. Moreover, phosphorylation of Ser 65 and Thr 70 alone was not sufficient to block the inhibition of mRNA translation by 4E-BP1, suggesting that multiple phosphorylation events must be combined to increase the rate of protein synthesis.[6]

Function

This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of cap-dependent mRNA translation.[7]

High level of phosphorylated 4E-BP1 has been widely reported in human cancers, and is associated with a worse outcome in several malignancies.[8]

Interactions

EIF4EBP1 has been shown to interact with:

References

  1. GRCh38: Ensembl release 89: ENSG00000187840 – Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000031490 – Ensembl, May 2017
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  7. EntrezGene 1978
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  18. Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, et al. (June 1999). "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism". Genes & Development. 13 (11): 1422–1437. doi:10.1101/gad.13.11.1422. PMC 316780. PMID 10364159.
  19. Connolly E, Braunstein S, Formenti S, Schneider RJ (May 2006). "Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells". Molecular and Cellular Biology. 26 (10): 3955–3965. doi:10.1128/MCB.26.10.3955-3965.2006. PMC 1489005. PMID 16648488.
  20. Shen X, Tomoo K, Uchiyama S, Kobayashi Y, Ishida T (October 2001). "Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods". Chemical & Pharmaceutical Bulletin. 49 (10). Tokyo: 1299–1303. doi:10.1248/cpb.49.1299. PMID 11605658.
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  22. Schalm SS, Fingar DC, Sabatini DM, Blenis J (May 2003). "TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function". Current Biology. 13 (10): 797–806. Bibcode:2003CBio...13..797S. doi:10.1016/s0960-9822(03)00329-4. PMID 12747827. S2CID 10326807.
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  25. Wang X, Beugnet A, Murakami M, Yamanaka S, Proud CG (April 2005). "Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins". Molecular and Cellular Biology. 25 (7): 2558–2572. doi:10.1128/MCB.25.7.2558-2572.2005. PMC 1061630. PMID 15767663.
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Further reading