EIF4G2 explained

Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the EIF4G2 gene.^{[1] [2]}

Function

Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by the eIF4G2 gene shares similarity with the C-terminal region of eIF4G1 that contains the binding sites for eIF4A and eIF3. eIF4G2 additionally contains a binding site for eIF4E at the N-terminus. Unlike eIF4G1, which supports cap-dependent and independent translation, the eIF4G2 gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.^[3]

Interactions

EIF4G2 has been shown to interact with EIF3A.^{[4] [5]}

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Shaughnessy JD, Jenkins NA, Copeland NG . cDNA cloning, expression analysis, and chromosomal localization of a gene with high homology to wheat eIF-(iso)4F and mammalian eIF-4G . Genomics . 39 . 2 . 192–7 . 1997 . 9027506 . 10.1006/geno.1996.4502 .
• Imataka H, Olsen HS, Sonenberg N . A new translational regulator with homology to eukaryotic translation initiation factor 4G . EMBO J. . 16 . 4 . 817–25 . 1997 . 9049310 . 1169682 . 10.1093/emboj/16.4.817 .
• Imataka H, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A . Mol. Cell. Biol. . 17 . 12 . 6940–7 . 1997 . 9372926 . 232551 . 10.1128/mcb.17.12.6940.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E . EMBO J. . 18 . 1 . 270–9 . 1999 . 9878069 . 1171121 . 10.1093/emboj/18.1.270 .
• Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK . Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G . Mol. Cell . 3 . 6 . 707–16 . 1999 . 10394359 . 10.1016/S1097-2765(01)80003-4 . free .
• Henis-Korenblit S, Strumpf NL, Goldstaub D, Kimchi A . A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation . Mol. Cell. Biol. . 20 . 2 . 496–506 . 2000 . 10611228 . 85113 . 10.1128/MCB.20.2.496-506.2000 .
• Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CU, Burley SK . A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery . Mol. Cell . 7 . 1 . 193–203 . 2001 . 11172724 . 10.1016/S1097-2765(01)00167-8 . free .
• Marissen WE, Gradi A, Sonenberg N, Lloyd RE . Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis . Cell Death Differ. . 7 . 12 . 1234–43 . 2000 . 11175261 . 10.1038/sj.cdd.4400750 . free .
• Asano K, Shalev A, Phan L, Nielsen K, Clayton J, Valásek L, Donahue TF, Hinnebusch AG . Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation . EMBO J. . 20 . 9 . 2326–37 . 2001 . 11331597 . 125443 . 10.1093/emboj/20.9.2326 .
• Pyronnet S, Dostie J, Sonenberg N . Suppression of cap-dependent translation in mitosis . Genes Dev. . 15 . 16 . 2083–93 . 2001 . 11511540 . 312759 . 10.1101/gad.889201 .
• Henis-Korenblit S, Shani G, Sines T, Marash L, Shohat G, Kimchi A . The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins . Proc. Natl. Acad. Sci. U.S.A. . 99 . 8 . 5400–5 . 2002 . 11943866 . 122781 . 10.1073/pnas.082102499 . free . 2002PNAS...99.5400H .
• Perales C, Carrasco L, Ventoso I . Cleavage of eIF4G by HIV-1 protease: effects on translation . FEBS Lett. . 533 . 1–3 . 89–94 . 2003 . 12505164 . 10.1016/S0014-5793(02)03764-X . 35982071 . free . 2003FEBSL.533...89P .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nat. Biotechnol. . 21 . 5 . 566–9 . 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Li Z, Hu CY, Mo BQ, Xu JD, Zhao Y . [Effect of beta-carotene on gene expression of breast cancer cells] . AI Zheng . 22 . 4 . 380–4 . 2003 . 12703993 .
• Qin H, Raught B, Sonenberg N, Goldstein EG, Edelman AM . Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I . J. Biol. Chem. . 278 . 49 . 48570–9 . 2003 . 14507913 . 10.1074/jbc.M308781200 . free .

Notes and References

1. Yamanaka S, Poksay KS, Arnold KS, Innerarity TL . A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme . Genes Dev. . 11 . 3 . 321–33 . March 1997 . 9030685 . 10.1101/gad.11.3.321 . free .
2. Levy-Strumpf N, Deiss LP, Berissi H, Kimchi A . DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death . Mol. Cell. Biol. . 17 . 3 . 1615–25 . March 1997 . 9032289 . 231887 . 10.1128/mcb.17.3.1615.
3. Web site: Entrez Gene: EIF4G2 eukaryotic translation initiation factor 4 gamma, 2.
4. Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N . A novel functional human eukaryotic translation initiation factor 4G . Mol. Cell. Biol. . 18 . 1 . 334–42 . January 1998 . 9418880 . 121501 . 10.1128/mcb.18.1.334.
5. Henis-Korenblit S, Strumpf NL, Goldstaub D, Kimchi A . A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation . Mol. Cell. Biol. . 20 . 2 . 496–506 . January 2000 . 10611228 . 85113 . 10.1128/MCB.20.2.496-506.2000 .