Alternatively Spliced Transcripts from the   Gene Produce Two Different Cap-binding Proteins

Lavoie, Cynthia; Lachance, Pascal E. D.; Sonenberg, Nahum; Lasko, Paul

doi:10.1074/jbc.271.27.16393

Cited by 32 publications

(34 citation statements)

References 30 publications

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“…15 However, the existence of additional or alternative phosphorylation sites cannot be ruled out. Interestingly, in cup mutant ovaries the expression of two eIF4E isoforms, arising from alternative splicing 16 and their overall phosphorylation, upon phosphatase treatment, appear to be changed when compared to wild-type. 6 This observation suggests that Cup may regulate eIF4E functions by modulating both its total amount and level of phosphorylation.…”

Section: Cup and The Phosphorylation Of Eif4ementioning

confidence: 97%

A Cup Full of Functions

Piccioni¹,

Zappavigna²,

Verrotti³

2005

RNA Biology

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Section: Cup and The Phosphorylation Of Eif4ementioning

confidence: 97%

A Cup Full of Functions

Piccioni¹,

Zappavigna²,

Verrotti³

2005

RNA Biology

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“…An 8.9-kb SpeI genomic fragment that includes eIF4E was obtained from a genomic clone (21) and was subcloned into pCaSpeR-4. This fragment contains approximately 4.9 kb of 5Ј flanking DNA upstream of eIF4E and about 1.0 kb of 3Ј flanking DNA.…”

Section: Fly Work Alleles L(3)589/11 (Eif4ementioning

confidence: 99%

“…An antibody specific to the phosphorylated form of Aplysia californica eIF4E was used to show a significant correlation between translation rates and increases in eIF4E phosphorylation in ganglion preparations (8). In Drosophila melanogaster, a gene encoding eIF4E was identified and mapped to polytene chromosome region 67A on the left arm of chromosome 3 (17,21). As for mammals, the phosphorylation of Drosophila eIF4E decreases upon heat shock concomitant with a decrease in translation rates (7).…”

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confidence: 99%

Phosphorylation of Eukaryotic Translation Initiation Factor 4E Is Critical for Growth

Lachance¹,

Miron

Raught

et al. 2002

Molecular and Cellular Biology

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161

146

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Eukaryotic translation initiation factor 4E (eIF4E) binds to the cap structure at the 5 end of mRNAs and is a critical target for the control of protein synthesis. eIF4E is phosphorylated in many systems in response to extracellular stimuli, but biochemical evidence to date has been equivocal as to the biological significance of this modification. Here we use a genetic approach to this problem. We show that, in Drosophila melanogaster, homozygous eIF4E mutants arrest growth during larval development. In Drosophila eIF4EI, Ser251 corresponds to Ser209 of mammalian eIF4E, which is phosphorylated in response to extracellular signals. We find that, in vivo, eIF4EI Ser251 mutants cannot incorporate labeled phosphate. Furthermore, transgenic Drosophila organisms expressing eIF4E Ser251Ala in an eIF4E mutant background have reduced viability. Escapers develop more slowly than control siblings and are smaller. These genetic data provide evidence that eIF4E phosphorylation is biologically significant and is essential for normal growth and development.Eukaryotic translation initiation factor 4E (eIF4E) is a ratelimiting component of translation initiation, and its activity is tightly regulated in cells (13,35). Regulation of eIF4E activity is critical to normal cell growth, as overexpression of eIF4E in rodent cells is oncogenic (22), while injection of eIF4E into quiescent NIH 3T3 cells induces DNA synthesis (38). In addition, Saccharomyces cerevisiae cells carrying the temperaturesensitive eIF4E allele cdc33ts4-2 arrest at the G 1 -to-S transition of the cell cycle (3) at the nonpermissive temperature, further implicating eIF4E in the regulation of proliferation.eIF4E is a subunit of complex eIF4F, which associates with the 5Ј end of the mRNA and facilitates the binding of the small ribosomal subunit and associated factors. In mammals, eIF4F consists of three subunits: eIF4E, eIF4A, and eIF4G (35). eIF4E binds to the 7-methyl-guanosine cap structure at the 5Ј end of the mRNA. The activity of eIF4E is regulated by two known mechanisms: the inhibitory eIF4E-binding proteins (4E-BPs) control the availability of eIF4E by competing for its binding with eIF4G (15, 25), while phosphorylation of eIF4E at a conserved serine is hypothesized to control its mRNA cap-binding activity (35).Unlike that of the 4E-BPs, the function of eIF4E phosphorylation is poorly understood. Unphosphorylated eIF4E can stimulate translation in vitro and can bind the mRNA cap or cap analogues, suggesting that phosphorylation is not strictly required for eIF4E function (35). However, when translation activity is altered by treatments with various extracellular stimuli, the phosphorylation state of eIF4E changes; in most cases, increased eIF4E phosphorylation correlates with increased translational activity. In contrast, eIF4E is hypophosphorylated during mitosis when the translation rate of mRNAs is low (1), and various cellular stresses such as heat shock and viral infection are correlated with reduced eIF4E phosphorylation (35). The major phosphorylat...

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“…Most eukaryotes have several paralogs of eIF4E (Hernández and Vazquez-Pianzola, 2005;Joshi et al, 2005), but the biological relevance of most of them is unknown. For example, Drosophila has eight eIF4E cognates Hernández et al, 1997;Hernández and Sierra, 1995;Lasko, 2000;Lavoie et al, 1996;Maroto and Sierra, 1989), but the biological functions of only eIF4E-1 (Gong et al, 2004;Graham et al, 2011;Hernández et al, 2004;Lachance et al, 2002;Menon et al, 2004;Ottone et al, 2011;Piccioni et al, 2005;Sigrist et al, 2000) and 4E-HP (Cho et al, 2005) have been characterized. Many of the eIF4E paralogs are expressed only in certain types of cells or during distinct developmental processes (Hernández and Vazquez-Pianzola, 2005).…”

Section: Introductionmentioning

confidence: 99%

Eukaryotic initiation factor 4E-3 is essential for meiotic chromosome segregation, cytokinesis and male fertility in Drosophila

et al. 2012

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SUMMARYGene expression is translationally regulated during many cellular and developmental processes. Translation can be modulated by affecting the recruitment of mRNAs to the ribosome, which involves recognition of the 5Ј cap structure by the cap-binding protein eIF4E. Drosophila has several genes encoding eIF4E-related proteins, but the biological role of most of them remains unknown. Here, we report that Drosophila eIF4E-3 is required specifically during spermatogenesis. Males lacking eIF4E-3 are sterile, showing defects in meiotic chromosome segregation, cytokinesis, nuclear shaping and individualization. We show that eIF4E-3 physically interacts with both eIF4G and eIF4G-2, the latter being a factor crucial for spermatocyte meiosis. In eIF4E-3 mutant testes, many proteins are present at different levels than in wild type, suggesting widespread effects on translation. Our results imply that eIF4E-3 forms specific eIF4F complexes that are essential for spermatogenesis.

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Alternatively Spliced Transcripts from the Gene Produce Two Different Cap-binding Proteins

Cited by 32 publications

References 30 publications

A Cup Full of Functions

A Cup Full of Functions

Phosphorylation of Eukaryotic Translation Initiation Factor 4E Is Critical for Growth

Eukaryotic initiation factor 4E-3 is essential for meiotic chromosome segregation, cytokinesis and male fertility in Drosophila

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