Eukaryotic translation initiation factor 4 gamma 1 explained

Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the EIF4G1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure, and recruitment of mRNA to the ribosome. Alternative splicing results in five transcript variants encoding four distinct isoforms.^[3] eIF4G serves as a scaffold, interacting with mRNA and the other components of the eIF4F complex, as well as the PABP and eIF3.

Interactions

Eukaryotic translation initiation factor 4 gamma has been shown to interact with MKNK1,^[4] EIF4A1,^{[5] [6] [7]} EIF4E,^{[6] [7] [8] [9] [10]} MKNK2^[11] and PABPC1.^[12]

See also

• Eukaryotic initiation factor

Further reading

• Gingras AC, Raught B, Sonenberg N . eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation . Annual Review of Biochemistry . 68 . 913–63 . 2000 . 10872469 . 10.1146/annurev.biochem.68.1.913 .
• Yan R, Rhoads RE . Human protein synthesis initiation factor eIF-4 gamma is encoded by a single gene (EIF4G) that maps to chromosome 3q27-qter . Genomics . 26 . 2 . 394–8 . Mar 1995 . 7601469 . 10.1016/0888-7543(95)80227-D .
• Mader S, Lee H, Pause A, Sonenberg N . 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 . Molecular and Cellular Biology . 15 . 9 . 4990–7 . Sep 1995 . 7651417 . 230746 . 10.1128/MCB.15.9.4990.
• Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N . Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function . Nature . 371 . 6500 . 762–7 . Oct 1994 . 7935836 . 10.1038/371762a0 . 1994Natur.371..762P . 4360955 .
• Lamphear BJ, Yan R, Yang F, Waters D, Liebig HD, Klump H, Kuechler E, Skern T, Rhoads RE . Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus . The Journal of Biological Chemistry . 268 . 26 . 19200–3 . Sep 1993 . 10.1016/S0021-9258(19)36499-3 . 8396129 . free .
• Haghighat A, Mader S, Pause A, Sonenberg N . Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E . The EMBO Journal . 14 . 22 . 5701–9 . Nov 1995 . 8521827 . 394685 . 10.1002/j.1460-2075.1995.tb00257.x.
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Lamphear BJ, Rhoads RE . A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases . Biochemistry . 35 . 49 . 15726–33 . Dec 1996 . 8961935 . 10.1021/bi961864t .
• Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E . Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma . Human Molecular Genetics . 6 . 1 . 33–9 . Jan 1997 . 9002667 . 10.1093/hmg/6.1.33 . free .
• Eberle J, Krasagakis K, Orfanos CE . Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human melanoma cells in vitro . International Journal of Cancer . 71 . 3 . 396–401 . May 1997 . 9139875 . 10.1002/(SICI)1097-0215(19970502)71:3<396::AID-IJC16>3.0.CO;2-E . 13458929 . free .
• Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N . A novel functional human eukaryotic translation initiation factor 4G . Molecular and Cellular Biology . 18 . 1 . 334–42 . Jan 1998 . 9418880 . 121501 . 10.1128/mcb.18.1.334.
• Piron M, Vende P, Cohen J, Poncet D . Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F . The EMBO Journal . 17 . 19 . 5811–21 . Oct 1998 . 9755181 . 1170909 . 10.1093/emboj/17.19.5811 .
• Imataka H, Gradi A, Sonenberg N . A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation . The EMBO Journal . 17 . 24 . 7480–9 . Dec 1998 . 9857202 . 1171091 . 10.1093/emboj/17.24.7480 .
• Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E . The EMBO Journal . 18 . 1 . 270–9 . Jan 1999 . 9878069 . 1171121 . 10.1093/emboj/18.1.270 .
• Laroia G, Cuesta R, Brewer G, Schneider RJ . Control of mRNA decay by heat shock-ubiquitin-proteasome pathway . Science . 284 . 5413 . 499–502 . Apr 1999 . 10205060 . 10.1126/science.284.5413.499 . 1999Sci...284..499L .
• Vary TC, Jefferson LS, Kimball SR . Amino acid-induced stimulation of translation initiation in rat skeletal muscle . The American Journal of Physiology . 277 . 6 Pt 1 . E1077–86 . Dec 1999 . 10600798 . 10.1152/ajpendo.1999.277.6.E1077. 4516850 .
• Cuesta R, Laroia G, Schneider RJ . Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes . Genes & Development . 14 . 12 . 1460–70 . Jun 2000 . 10.1101/gad.14.12.1460 . 10859165 . 316692 .
• Chartier-Harlin MC, Dachsel JC, Vilariño-Güell C, Lincoln SJ, Leprêtre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destée A, Farrer MJ . Translation initiator EIF4G1 mutations in familial Parkinson disease . American Journal of Human Genetics . 89 . 3 . 398–406 . Sep 2011 . 21907011 . 10.1016/j.ajhg.2011.08.009 . 3169825.

Notes and References

1. Yan R, Rychlik W, Etchison D, Rhoads RE . Amino acid sequence of the human protein synthesis initiation factor eIF-4 gamma . The Journal of Biological Chemistry . 267 . 32 . 23226–31 . Nov 1992 . 10.1016/S0021-9258(18)50080-6 . 1429670 . free .
2. Imataka H, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A . Molecular and Cellular Biology . 17 . 12 . 6940–7 . Dec 1997 . 9372926 . 232551 . 10.1128/mcb.17.12.6940.
3. Web site: Entrez Gene: EIF4G1 eukaryotic translation initiation factor 4 gamma, 1.
4. Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E . The EMBO Journal . 18 . 1 . 270–9 . Jan 1999 . 9878069 . 1171121 . 10.1093/emboj/18.1.270 .
5. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
6. Connolly E, Braunstein S, Formenti S, Schneider RJ . 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 . 3955–65 . May 2006 . 16648488 . 1489005 . 10.1128/MCB.26.10.3955-3965.2006 .
7. Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence JC . mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin . The EMBO Journal . 25 . 8 . 1659–68 . Apr 2006 . 16541103 . 1440840 . 10.1038/sj.emboj.7601047 .
8. Vary TC, Jefferson LS, Kimball SR . Amino acid-induced stimulation of translation initiation in rat skeletal muscle . The American Journal of Physiology . 277 . 6 Pt 1 . E1077–86 . Dec 1999 . 10600798 . 10.1152/ajpendo.1999.277.6.E1077 . 4516850 .
9. Mader S, Lee H, Pause A, Sonenberg N . 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 . Molecular and Cellular Biology . 15 . 9 . 4990–7 . Sep 1995 . 7651417 . 230746 . 10.1128/MCB.15.9.4990 .
10. Kumar V, Sabatini D, Pandey P, Gingras AC, Majumder PK, Kumar M, Yuan ZM, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S . 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 . The Journal of Biological Chemistry . 275 . 15 . 10779–87 . Apr 2000 . 10753870 . 10.1074/jbc.275.15.10779 . free .
11. Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG . The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization . Molecular and Cellular Biology . 23 . 16 . 5692–705 . Aug 2003 . 12897141 . 166352 . 10.1128/MCB.23.16.5692-5705.2003 .
12. Imataka H, Gradi A, Sonenberg N . A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation . The EMBO Journal . 17 . 24 . 7480–9 . Dec 1998 . 9857202 . 1171091 . 10.1093/emboj/17.24.7480 .