EIF4E

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Eukaryotic translation initiation factor 4E
Protein EIF4E PDB 1ej1.png
PDB rendering based on 1ej1.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols EIF4E ; AUTS19; CBP; EIF4E1; EIF4EL1; EIF4F
External IDs OMIM133440 MGI95305 HomoloGene123817 ChEMBL: 4848 GeneCards: EIF4E Gene
RNA expression pattern
PBB GE EIF4E 201436 at tn.png
PBB GE EIF4E 201435 s at tn.png
PBB GE EIF4E 201437 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1977 13684
Ensembl ENSG00000151247 ENSMUSG00000028156
UniProt P06730 P63073
RefSeq (mRNA) NM_001130678 NM_007917
RefSeq (protein) NP_001124150 NP_031943
Location (UCSC) Chr 4:
99.79 – 99.85 Mb
Chr 3:
138.53 – 138.56 Mb
PubMed search [1] [2]

Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the EIF4E gene.[1][2]

Function[edit]

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, the most notable being heat shock proteins, do not require eIF4E in order to be translated. Both viruses and cellular proteins achieve this through an IRES structure in the RNA.

FMRP represses translation through EIF4E binding[edit]

Fragile X mental retardation protein (FMR1) acts to regulate translation of specific mRNAs through its binding of eIF4E. FMRP acts by binding CYFIP1, which directly binds eIF4e at a domain that is structurally similar to those found in 4E-BPs including EIF4EBP3, EIF4EBP1, and EIF4EBP2. The FMRP/CYFIP1 complex binds in such a way as to prevent the eIF4E-eIF4G interaction, which is necessary for translation to occur. The FMRP/CYFIP1/eIF4E interaction is strengthened by the presence of mRNA(s). In particular, BC1 RNA allows for an optimal interaction between FMRP and CYFIP1.[5] RNA-BC1 is a non-translatable, dendritic mRNA, which binds FMRP to allow for its association with a specific target mRNA. BC1 may function to regulate FMRP and mRNA interactions at synapse(s) through its recruitment of FMRP to the appropriate mRNA.[6] In addition, FMRP may recruit CYFIP1 to specific mRNAs in order to repress translation. The FMRP-CYFIP1 translational inhibitor is regulated by stimulation of neuron(s). Increased synaptic stimulation resulted in the dissociation of eIF4E and CYFIP1, allowing for the initiation of translation.[5]

Interactions[edit]

EIF4E has been shown to interact with EIF4A1,[7][8] EIF4EBP3,[9][10] EIF4EBP1,[7][8][11][12][13][14][15][16][17][18][19][20][21] EIF4EBP2,[12][22] Eukaryotic translation initiation factor 4 gamma,[8][12][17][23][24] EIF4G2[25] and EIF4ENIF1.[26]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. PMC 304336. PMID 3469651. 
  4. ^ "Entrez Gene: eIF4E Eukaryotic translation initiation factor 4E". 
  5. ^ a b Napoli, I.; Mercaldo, V.; Boyl, P. P.; Eleuteri, B.; Zalfa, F.; De Rubeis, S.; Di Marino, D.; Mohr, E.; Massimi, M.; Falconi, M.; Witke, W.; Costa-Mattioli, M.; Sonenberg, N.; Achsel, T.; Bagni, C. (2008). "The Fragile X Syndrome Protein Represses Activity-Dependent Translation through CYFIP1, a New 4E-BP". Cell 134 (6): 1042–1054. doi:10.1016/j.cell.2008.07.031. PMID 18805096.  edit
  6. ^ Zalfa, F.; Giorgi, M.; Primerano, B.; Moro, A.; Di Penta, A.; Reis, S.; Oostra, B.; Bagni, C. (2003). "The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses". Cell 112 (3): 317–327. doi:10.1016/S0092-8674(03)00079-5. PMID 12581522.  edit
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  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): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
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  14. ^ 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): 757–66. doi:10.1111/j.1365-2443.2006.00977.x. ISSN 1356-9597. PMID 16824195. 
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  16. ^ 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): 3076–85. doi:10.1046/j.1432-1033.2002.02992.x. ISSN 0014-2956. PMID 12071973. 
  17. ^ 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 (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): 10779–87. doi:10.1074/jbc.275.15.10779. ISSN 0021-9258. PMID 10753870. 
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External links[edit]

Further reading[edit]

  • 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. doi:10.4161/cc.6.1.3688. PMID 17245113. 
  • Malys N, McCarthy JEG (2010). "Translation initiation: variations in the mechanism can be anticipated". Cellular and Molecular Life Sciences 68 (6): 991–1003. doi:10.1007/s00018-010-0588-z. PMID 21076851. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.