Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein which in humans is encoded by the eIF4E gene.[1][2]
Function
All eukaryotic cellular mRNAs are blocked at their 5-prime ends with the 7-methyl-guanosine cap structure, m7GpppX (where X is any nucleotide). This structure is involved in several cellular processes including enhanced translational efficiency, splicing, mRNA stability, and RNA nuclear export. EIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of a multiprotein complex termed EIF4F. The EIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of EIF4F are a 50-kD polypeptide, termed EIF4A, that possesses ATPase and RNA helicase activities, and a 220-kD polypeptide, EIF4G.[3][4]
eIF4E's function is to bind an mRNA cap and ultimately bring it to the ribosome. eIF4E is part of the eIF4F pre-initiation complex; which is made up of eIF4E, and eIF4G (eIF4F is sometimes considered to have additional protein components). Almost all cellular proteins require eIF4E in order to be translated into protein. eIF4E binds the first nucleotide on the 5' end of an mRNA molecule (known as the cap): a 7 methyl guanosine (m7G). It sandwiches m7G between 2 tryptophan residues, and other amino acids are involved in the binding.
Some viruses cut eIF4G in such a way that the eIF4E binding site is removed and the virus is able to translate its proteins without eIF4E. Also some cellular proteins, most notably heat shock proteins, don't require eIF4E in order to be translated. Both viruses and cellular proteins achieve this through an IRES structure in the RNA.
Interactions
EIF4E has been shown to interact with EIF4A1,[5][6] EIF4EBP3,[7][8] EIF4EBP1,[9][5][10][11][12][13][14][15][16][17][6][18][19] EIF4EBP2,[10][20] Eukaryotic translation initiation factor 4 gamma,[21][10][6][22][15] EIF4G2[23] and EIF4ENIF1.[24]
See also
References
- ^ Pelletier J, Brook JD, Housman DE (August 1991). "Assignment of two of the translation initiation factor-4E (EIF4EL1 and EIF4EL2) genes to human chromosomes 4 and 20". Genomics 10 (4): 1079–82. doi:10.1016/0888-7543(91)90203-Q. PMID 1916814.
- ^ Jones RM, MacDonald ME, Branda J, Altherr MR, Louis DN, Schmidt EV (May 1997). "Assignment of the human gene encoding eukaryotic initiation factor 4E (EIF4E) to the region q21-25 on chromosome 4". Somat. Cell Mol. Genet. 23 (3): 221–3. doi:10.1007/BF02721373. PMID 9330633.
- ^ Rychlik W, Domier LL, Gardner PR, Hellmann GM, Rhoads RE (February 1987). "Amino acid sequence of the mRNA cap-binding protein from human tissues". Proc. Natl. Acad. Sci. U.S.A. 84 (4): 945–9. doi:10.1073/pnas.84.4.945. PMID 3469651. PMC 304336. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3469651.
- ^ "Entrez Gene: eIF4E Eukaryotic translation initiation factor 4E". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1977.
- ^ a b 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: 89. doi:10.1038/msb4100134. PMID 17353931.
- ^ a b c 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): 3955–65. doi:10.1128/MCB.26.10.3955-3965.2006. ISSN 0270-7306. PMID 16648488.
- ^ Kleijn, Miranda; Scheper Gert C, Wilson Mary L, Tee Andrew R, Proud Christopher G (Dec. 2002). "Localisation and regulation of the eIF4E-binding protein 4E-BP3". FEBS Lett. (Netherlands) 532 (3): 319–23. ISSN 0014-5793. PMID 12482586.
- ^ Poulin, F; Gingras A C, Olsen H, Chevalier S, Sonenberg N (May. 1998). "4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family". J. Biol. Chem. (UNITED STATES) 273 (22): 14002–7. ISSN 0021-9258. PMID 9593750.
- ^ 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 (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- ^ a b c Mader, S; Lee H, Pause A, Sonenberg N (Sep. 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. PMID 7651417.
- ^ Rao, Ravi D; Mladek Ann C, Lamont Jeffrey D, Goble Jennie M, Erlichman Charles, James C David, Sarkaria Jann N (Oct. 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): 921–9. ISSN 1522-8002. PMID 16242075.
- ^ Eguchi, Satoshi; Tokunaga Chiharu, Hidayat Sujuti, Oshiro Noriko, Yoshino Ken-ichi, Kikkawa Ushio, Yonezawa Kazuyoshi (Jul. 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): 757–66. doi:10.1111/j.1365-2443.2006.00977.x. ISSN 1356-9597. PMID 16824195.
- ^ Yang, D; Brunn G J, Lawrence J C (Jun. 1999). "Mutational analysis of sites in the translational regulator, PHAS-I, that are selectively phosphorylated by mTOR". FEBS Lett. (NETHERLANDS) 453 (3): 387–90. ISSN 0014-5793. PMID 10405182.
- ^ Patel, Jashmin; McLeod Laura E, Vries Robert G J, Flynn Andrea, Wang Xuemin, Proud Christopher G (Jun. 2002). "Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors". Eur. J. Biochem. (Germany) 269 (12): 3076–85. ISSN 0014-2956. PMID 12071973.
- ^ a b 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 (Apr. 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): 10779–87. ISSN 0021-9258. PMID 10753870.
- ^ Kumar, V; Pandey P, Sabatini D, Kumar M, Majumder P K, Bharti A, Carmichael G, Kufe D, Kharbanda S (Mar. 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): 1087–97. doi:10.1093/emboj/19.5.1087. ISSN 0261-4189. PMID 10698949.
- ^ Gingras, A C; Gygi S P, Raught B, Polakiewicz R D, Abraham R T, Hoekstra M F, Aebersold R, Sonenberg N (Jun. 1999). "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism". Genes Dev. (UNITED STATES) 13 (11): 1422–37. ISSN 0890-9369. PMID 10364159.
- ^ Shen, X; Tomoo K, Uchiyama S, Kobayashi Y, Ishida T (Oct. 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): 1299–303. ISSN 0009-2363. PMID 11605658.
- ^ Adegoke, Olasunkanmi A J; Chevalier Stéphanie, Morais José A, Gougeon Réjeanne, Kimball Scot R, Jefferson Leonard S, Wing Simon S, Marliss Errol B (Jan. 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): E105-13. doi:10.1152/ajpendo.90752.2008. ISSN 0193-1849. PMID 18957614.
- ^ Pause, A; Belsham G J, Gingras A C, Donzé O, Lin T A, Lawrence J C, Sonenberg N (Oct. 1994). "Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function". Nature (ENGLAND) 371 (6500): 762–7. doi:10.1038/371762a0. ISSN 0028-0836. PMID 7935831.
- ^ Vary, T C; Jefferson L S, Kimball S R (Dec. 1999). "Amino acid-induced stimulation of translation initiation in rat skeletal muscle". Am. J. Physiol. (UNITED STATES) 277 (6 Pt 1): E1077-86. ISSN 0002-9513. PMID 10600798.
- ^ Harris, Thurl E; Chi An, Shabanowitz Jeffrey, Hunt Donald F, Rhoads Robert E, Lawrence John C (Apr. 2006). "mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin". EMBO J. (England) 25 (8): 1659–68. doi:10.1038/sj.emboj.7601047. ISSN 0261-4189. PMID 16541103.
- ^ Gradi, A; Imataka H, Svitkin Y V, Rom E, Raught B, Morino S, Sonenberg N (Jan. 1998). "A novel functional human eukaryotic translation initiation factor 4G". Mol. Cell. Biol. (UNITED STATES) 18 (1): 334–42. ISSN 0270-7306. PMID 9418880.
- ^ Dostie, J; Ferraiuolo M, Pause A, Adam S A, Sonenberg N (Jun. 2000). "A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5' cap-binding protein, eIF4E". EMBO J. (ENGLAND) 19 (12): 3142–56. doi:10.1093/emboj/19.12.3142. ISSN 0261-4189. PMID 10856257.
External links
Further reading
- Jain S, Khuri FR, Shin DM (2004). "Prevention of head and neck cancer: current status and future prospects.". Current problems in cancer 28 (5): 265–86. doi:10.1016/j.currproblcancer.2004.05.003. PMID 15375804.
- Culjkovic B, Topisirovic I, Borden KL (2007). "Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E.". Cell Cycle 6 (1): 65–9. PMID 17245113.
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PDB Gallery |
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1ej1: COCRYSTAL STRUCTURE OF THE MESSENGER RNA 5' CAP-BINDING PROTEIN (EIF4E) BOUND TO 7-METHYL-GDP
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1ej4: COCRYSTAL STRUCTURE OF EIF4E/4E-BP1 PEPTIDE
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1ejh: EIF4E/EIF4G PEPTIDE/7-METHYL-GDP
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1ipb: CRYSTAL STRUCTURE OF EUKARYOTIC INITIATION FACTOR 4E COMPLEXED WITH 7-METHYL GPPPA
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1ipc: CRYSTAL STRUCTURE OF EUKARYOTIC INITIATION FACTOR 4E COMPLEXED WITH 7-METHYL GTP
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1l8b: Cocrystal Structure of the Messenger RNA 5' Cap-binding Protein (eIF4E) bound to 7-methylGpppG
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1wkw: Crystal structure of the ternary complex of eIF4E-m7GpppA-4EBP1 peptide
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2gpq: Cap-free structure of eIF4E suggests basis for its allosteric regulation
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Protein biosynthesis: translation (prokaryotic, eukaryotic) |
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| Ribosomal proteins |
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Archaeal
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aIF1 aIF2 aIF5 aIF6
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eIF1 (AX, AY, 1B)
eIF2 (α, β, γ)
eIF3 (A, B, C, D, F, G, H, I, J, K, M, S6)
eIF4 (A2, A3, B, E1, E2, G1, G2, G3, H)
eIF5 (A, A2, B)
eIF6
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Other
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| Other concepts |
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