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Eukaryotic translation initiation factor 4E binding protein 1

Rendering of 1WKW
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols EIF4EBP1 ; 4E-BP1; 4EBP1; BP-1; PHAS-I
External IDs OMIM602223 MGI103267 HomoloGene3021 GeneCards: EIF4EBP1 Gene
RNA expression pattern
PBB GE EIF4EBP1 221539 at tn.png
More reference expression data
Species Human Mouse
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:
37.89 – 37.92 Mb
Chr 8:
27.26 – 27.28 Mb
PubMed search [1] [2]

Eukaryotic translation initiation factor 4E-binding protein 1 is a protein that in humans is encoded by the EIF4EBP1 gene.[1]

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 mRNA translation.[2]


EIF4EBP1 has been shown to interact with Mammalian target of rapamycin,[3][4][5][6][7][8][9][10] EIF4E[11][12][13][14][15][16][17][18][19][20][21][22][23] and KIAA1303.[3][6][9][10][15][24][25][26]


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  2. ^ "Entrez Gene: EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1". 
  3. ^ a b Schalm, Stefanie S; Fingar Diane C, Sabatini David M, Blenis John (May 2003). "TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function". Curr. Biol. (England) 13 (10): 797–806. doi:10.1016/S0960-9822(03)00329-4. ISSN 0960-9822. PMID 12747827. 
  4. ^ Kim, Do-Hyung; Sarbassov D D, Ali Siraj M, King Jessie E, Latek Robert R, Erdjument-Bromage Hediye, Tempst Paul, Sabatini David M (July 2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery". Cell (United States) 110 (2): 163–175. doi:10.1016/S0092-8674(02)00808-5. ISSN 0092-8674. PMID 12150925. 
  5. ^ Long, Xiaomeng; Lin Yenshou, Ortiz-Vega Sara, Yonezawa Kazuyoshi, Avruch Joseph (April 2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. (England) 15 (8): 702–713. doi:10.1016/j.cub.2005.02.053. ISSN 0960-9822. PMID 15854902. 
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  7. ^ Takahashi, T; Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K (September 2000). "Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro". Genes Cells (ENGLAND) 5 (9): 765–775. doi:10.1046/j.1365-2443.2000.00365.x. ISSN 1356-9597. PMID 10971657. 
  8. ^ Burnett, P E; Barrow R K, Cohen N A, Snyder S H, Sabatini D M (February 1998). "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (4): 1432–1437. doi:10.1073/pnas.95.4.1432. ISSN 0027-8424. PMC 19032. PMID 9465032. 
  9. ^ a b Wang, Lifu; Rhodes Christopher J, Lawrence John C (August 2006). "Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1". J. Biol. Chem. (United States) 281 (34): 24293–24303. doi:10.1074/jbc.M603566200. ISSN 0021-9258. PMID 16798736. 
  10. ^ a b Wang, Xuemin; Beugnet Anne, Murakami Mirei, Yamanaka Shinya, Proud Christopher G (April 2005). "Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins". Mol. Cell. Biol. (United States) 25 (7): 2558–2572. doi:10.1128/MCB.25.7.2558-2572.2005. ISSN 0270-7306. PMC 1061630. PMID 15767663. 
  11. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514. 
  12. ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. 
  13. ^ Mader, S; Lee H, Pause A, Sonenberg N (September 1995). "The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins". Mol. Cell. Biol. (UNITED STATES) 15 (9): 4990–7. ISSN 0270-7306. PMC 230746. PMID 7651417. 
  14. ^ Rao, Ravi D; Mladek Ann C, Lamont Jeffrey D, Goble Jennie M, Erlichman Charles, James C David, Sarkaria Jann N (October 2005). "Disruption of parallel and converging signaling pathways contributes to the synergistic antitumor effects of simultaneous mTOR and EGFR inhibition in GBM cells". Neoplasia (United States) 7 (10): 921–929. doi:10.1593/neo.05361. ISSN 1522-8002. PMC 1502028. PMID 16242075. 
  15. ^ a b Eguchi, Satoshi; Tokunaga Chiharu, Hidayat Sujuti, Oshiro Noriko, Yoshino Ken-ichi, Kikkawa Ushio, Yonezawa Kazuyoshi (July 2006). "Different roles for the TOS and RAIP motifs of the translational regulator protein 4E-BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size". Genes Cells (England) 11 (7): 757–766. doi:10.1111/j.1365-2443.2006.00977.x. ISSN 1356-9597. PMID 16824195. 
  16. ^ Yang, D; Brunn G J, Lawrence J C (June 1999). "Mutational analysis of sites in the translational regulator, PHAS-I, that are selectively phosphorylated by mTOR". FEBS Lett. (NETHERLANDS) 453 (3): 387–390. doi:10.1016/S0014-5793(99)00762-0. ISSN 0014-5793. PMID 10405182. 
  17. ^ Patel, Jashmin; McLeod Laura E, Vries Robert G J, Flynn Andrea, Wang Xuemin, Proud Christopher G (June 2002). "Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors". Eur. J. Biochem. (Germany) 269 (12): 3076–3085. doi:10.1046/j.1432-1033.2002.02992.x. ISSN 0014-2956. PMID 12071973. 
  18. ^ Kumar, V; Sabatini D, Pandey P, Gingras A C, Majumder P K, Kumar M, Yuan Z M, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S (April 2000). "Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase". J. Biol. Chem. (UNITED STATES) 275 (15): 10779–10787. doi:10.1074/jbc.275.15.10779. ISSN 0021-9258. PMID 10753870. 
  19. ^ Kumar, V; Pandey P, Sabatini D, Kumar M, Majumder P K, Bharti A, Carmichael G, Kufe D, Kharbanda S (March 2000). "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation". EMBO J. (ENGLAND) 19 (5): 1087–1097. doi:10.1093/emboj/19.5.1087. ISSN 0261-4189. PMC 305647. PMID 10698949. 
  20. ^ Gingras, A C; Gygi S P, Raught B, Polakiewicz R D, Abraham R T, Hoekstra M F, Aebersold R, Sonenberg N (June 1999). "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism". Genes Dev. (UNITED STATES) 13 (11): 1422–1437. doi:10.1101/gad.13.11.1422. ISSN 0890-9369. PMC 316780. PMID 10364159. 
  21. ^ Connolly, Eileen; Braunstein Steve, Formenti Silvia, Schneider Robert J (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". Mol. Cell. Biol. (United States) 26 (10): 3955–3965. doi:10.1128/MCB.26.10.3955-3965.2006. ISSN 0270-7306. PMC 1489005. PMID 16648488. 
  22. ^ 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". Chem. Pharm. Bull. (Japan) 49 (10): 1299–1303. doi:10.1248/cpb.49.1299. ISSN 0009-2363. PMID 11605658. 
  23. ^ Adegoke, Olasunkanmi A J; Chevalier Stéphanie, Morais José A, Gougeon Réjeanne, Kimball Scot R, Jefferson Leonard S, Wing Simon S, Marliss Errol B (January 2009). "Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men". Am. J. Physiol. Endocrinol. Metab. (United States) 296 (1): E105–E113. doi:10.1152/ajpendo.90752.2008. ISSN 0193-1849. PMC 2636991. PMID 18957614. 
  24. ^ Ha, Sang Hoon; Kim Do-Hyung, Kim Il-Shin, Kim Jung Hwan, Lee Mi Nam, Lee Hyun Ju, Kim Jong Heon, Jang Sung Key, Suh Pann-Ghill, Ryu Sung Ho (December 2006). "PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals". Cell. Signal. (England) 18 (12): 2283–2291. doi:10.1016/j.cellsig.2006.05.021. ISSN 0898-6568. PMID 16837165. 
  25. ^ Beugnet, Anne; Wang Xuemin, Proud Christopher G (October 2003). "Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1". J. Biol. Chem. (United States) 278 (42): 40717–40722. doi:10.1074/jbc.M308573200. ISSN 0021-9258. PMID 12912989. 
  26. ^ Nojima, Hiroki; Tokunaga Chiharu, Eguchi Satoshi, Oshiro Noriko, Hidayat Sujuti, Yoshino Ken-ichi, Hara Kenta, Tanaka Noriaki, Avruch Joseph, Yonezawa Kazuyoshi (May 2003). "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif". J. Biol. Chem. (United States) 278 (18): 15461–15464. doi:10.1074/jbc.C200665200. ISSN 0021-9258. PMID 12604610. 

Further reading[edit]