Disease relevance of eIF4E-7

• In contrast to Thor, Drosophila eIF4E is not induced by bacterial infection [1].
• The pvr2 locus in pepper codes for a eukaryotic translation initiation factor 4E (eIF4E) gene that confers resistance to viruses belonging to the potyvirus genus [2].

High impact information on eIF4E-7

• Thus, d4E-BP is an important downstream effector of a dFOXO phenotype, and regulation of translation by eIF4E is vital during environmental stress [3].
• Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP [3].
• We furthermore show that cup and eIF4E interact genetically, because a reduction in the level of eIF4E activity deteriorates the development and growth of ovaries bearing homozygous cup mutant alleles [4].
• Cup is required for the correct accumulation and localization of eIF4E within the posterior cytoplasm of developing oocytes [4].
• We generated lk6 loss-of-function alleles and found that eIF4E phosphorylation is dramatically reduced in lk6 mutants [5].

Biological context of eIF4E-7

• In Drosophila mutant embryos devoid of the eukaryotic initiation factor 4E (eIF4E), reaper transcription is induced and apoptosis proceeds [6].
• Several potential binding sites for MADS box transcription factors within the 5' flanking region of eIF4E genes from the three plant species were also predicted [2].
• The eIF4E gene is organised into five exons and four introns and showed a strictly conserved exon/intron structure with eIF4E genes from Arabidopsis thaliana and rice [2].
• Analysis of a set of cDNA clones encoding eIF4E led to the conclusion that the two different protein isoforms, which we term eIF4EI and eIF4EII, result from three alternatively spliced transcripts from a single eIF4E gene, which maps to region 67A8-B2 on polytene chromosomes [7].
• Drosophila cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis [8].

Associations of eIF4E-7 with chemical compounds

• To overcome this protective mechanism, we introduced alanine substitutions at four phosphorylation/inactivation sites in 4EBP1 to constitutively activate a 4EBP mu to block eIF4E [9].

References