Contrasting mechanisms of regulating translation of specific Drosophila germline mRNAs at the level of 5′-cap structure binding

2005 ◽  
Vol 33 (6) ◽  
pp. 1544-1546 ◽  
Author(s):  
P. Lasko ◽  
P. Cho ◽  
F. Poulin ◽  
N. Sonenberg
Keyword(s):  
Translational Control ◽  
Binding Proteins ◽  
Regulatory Mechanism ◽  
Ribosomal Subunit ◽  
Drosophila Embryo ◽  
Initiation Factor ◽  
Control Mechanisms ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
Cognate Protein

Translational control is a key genetic regulatory mechanism underlying the initial establishment of the major spatial axes of the Drosophila embryo. Many translational control mechanisms target eIF4E (eukaryotic initiation factor 4E), an initiation factor that recognizes the 5′-cap structure of the mRNA. Cap recognition by eIF4E, in complex with eIF4G, is essential for recruitment of the mRNA to the small ribosomal subunit. One established mechanism for repressing translation involves eIF4E-binding proteins, which competitively inhibit the eIF4E–eIF4G interaction. Our group has uncovered a novel mechanism for repression in which an eIF4E cognate protein called d4EHP, which cannot bind eIF4G, binds to the 5′-cap structure of cad mRNA thus rendering it translationally inactive. These two related, but distinct, mechanisms are discussed and contrasted in this review.

Tissue Distribution, Genomic Structure, and Chromosome Mapping of Mouse and Human Eukaryotic Initiation Factor 4E-Binding Proteins 1 and 2

Genomics ◽  
1996 ◽  
Vol 38 (3) ◽  
pp. 353-363 ◽  
Author(s):  
Kyoko Tsukiyama-Kohara ◽  
Silvia M. Vidal ◽  
Anne-Claude Gingras ◽  
Thomas W. Glover ◽  
Samir M. Hanash ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Binding Proteins ◽  
Genomic Structure ◽  
Chromosome Mapping ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

scholarly journals 4E-binding Proteins, the Suppressors of Eukaryotic Initiation Factor 4E, Are Down-regulated in Cells with Acquired or Intrinsic Resistance to Rapamycin

2002 ◽  
Vol 277 (16) ◽  
pp. 13907-13917 ◽  
Author(s):  
Michael B. Dilling ◽  
Glen S. Germain ◽  
Lorina Dudkin ◽  
Arun L. Jayaraman ◽  
Xiongwen Zhang ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Intrinsic Resistance ◽  
Eukaryotic Initiation Factor 4E ◽  
In Cells

Translational Control Through the eIF4E Binding Proteins in the Brain

2018 ◽  
Author(s):  
Argel Aguilar-Valles ◽  
Edna Matta-Camacho ◽  
Nahum Sonenberg
Keyword(s):  
Translational Control ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Depressive Disorders ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
Initiation Step ◽  
The Brain

Translation of messenger RNA (mRNA) into protein (protein synthesis) is a highly regulated process that controls gene expression. Various signaling pathways, including the mammalian target of rapamycin (mTOR), control mRNA translation at the initiation step. mTOR is part of a multi-subunit complex that regulates mRNA translation initiation by phosphorylating and inactivating the eukaryotic initiation factor 4E binding proteins (4E-BPs). 4E-BPs are a central mechanism in the control of cap-dependent translation in the brain. This chapter reviews the involvement of the 4E-BPs, particularly 4E-BP2, in brain development and synaptic transmission. Furthermore, it discusses the involvement of 4E-BP2 in autistic-like alterations, learning and memory, circadian rhythm regulation, and its roles in the pathophysiology and treatment of psychiatric (depressive disorders, schizophrenia) and neurodegenerative disorders (Parkinson’s).

eIF4E-binding proteins: new factors, new locations, new roles

2014 ◽  
Vol 42 (4) ◽  
pp. 1238-1245 ◽  
Author(s):  
Anastasiia Kamenska ◽  
Clare Simpson ◽  
Nancy Standart
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Ribosomal Subunit ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
New Locations ◽  
Specific Mrnas

The cap-binding translation initiation factor eIF4E (eukaryotic initiation factor 4E) is central to protein synthesis in eukaryotes. As an integral component of eIF4F, a complex also containing the large bridging factor eIF4G and eIF4A RNA helicase, eIF4E enables the recruitment of the small ribosomal subunit to the 5′ end of mRNAs. The interaction between eIF4E and eIF4G via a YXXXXLϕ motif is regulated by small eIF4E-binding proteins, 4E-BPs, which use the same sequence to competitively bind eIF4E thereby inhibiting cap-dependent translation. Additional eIF4E-binding proteins have been identified in the last 10–15 years, characterized by the YXXXXLϕ motif, and by interactions (many of which remain to be detailed) with RNA-binding proteins, or other factors in complexes that recognize the specific mRNAs. In the present article, we focus on the metazoan 4E-T (4E-transporter)/Cup family of eIF4E-binding proteins, and also discuss very recent examples in yeast, fruitflies and humans, some of which predictably inhibit translation, while others may result in mRNA decay or even enhance translation; altogether considerably expanding our understanding of the roles of eIF4E-binding proteins in gene expression regulation.

scholarly journals Transcriptional and translational control of ornithine decarboxylase during Ras transformation

2004 ◽  
Vol 377 (1) ◽  
pp. 257-264 ◽  
Author(s):  
Lisa M. SHANTZ
Keyword(s):  
Ornithine Decarboxylase ◽  
Translational Control ◽  
Initiation Factor ◽  
Decarboxylase Activity ◽  
Eukaryotic Initiation Factor ◽  
Loss Of Function ◽  
Partial Loss ◽  
Eukaryotic Initiation Factor 4E ◽  
Phosphoinositide 3 Kinase ◽  
Constitutively Active

ODC (ornithine decarboxylase) activity is induced following ras activation. However, the Ras effector pathways responsible are unknown. These experiments used NIH-3T3 cells expressing partial-loss-of-function Ras mutants to activate selectively pathways downstream of Ras and examined the contribution of each pathway to ODC induction. Overexpression of Ras12V, a constitutively active mutant, resulted in ODC activities up to 20-fold higher than controls. Stable transfections of Ras partial-loss-of-function mutants and constitutively active forms of MEK (MAPK kinase) and Akt indicated that activation of more than one Ras effector pathway is necessary for the complete induction of ODC activity. The increase in ODC activity in Ras12V-transformed cells is not owing to a substantial change in ODC protein half-life, which increased by <2-fold. Northern-blot analysis and reporter assays suggested that the mechanism of ODC induction involves both a modest increase in the transcription of ODC mRNA and a much more considerable increase in the translation of mRNA into protein. ODC transcription was controlled through a pathway dependent on Raf/MEK/ERK (where ERK stands for extracellular-signal-regulated kinase) activation, whereas activation of the phosphoinositide 3-kinase and the Raf/MEK/ERK pathways were necessary for translational regulation of ODC. The increase in ODC synthesis was accompanied by changes in phosphorylation of eukaryotic initiation factor 4E and its binding protein 4E-BP1. Results show that the phosphoinositide 3-kinase pathway regulates phosphorylation of both proteins, whereas the Raf/MEK/ERK pathway affects only the eukaryotic initiation factor 4E phosphorylation.

scholarly journals The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response

2009 ◽  
Vol 296 (5) ◽  
pp. C1207-C1217 ◽  
Author(s):  
R. Sukarieh ◽  
N. Sonenberg ◽  
J. Pelletier
Keyword(s):  
Protein Synthesis ◽  
Binding Proteins ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Repressor Proteins ◽  
Shock Response ◽  
Rate Limiting

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E.

scholarly journals Translational Control by Neuroguidin, a Eukaryotic Initiation Factor 4E and CPEB Binding Protein

2006 ◽  
Vol 26 (11) ◽  
pp. 4277-4287 ◽  
Author(s):  
Mi-Young Jung ◽  
Lori Lorenz ◽  
Joel D. Richter
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Neural Development ◽  
Translational Control ◽  
Binding Protein ◽  
Neural Tube Closure ◽  
Initiation Factor ◽  
Dependent Manner ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

ABSTRACT CPEB-mediated translation is important in early development and neuronal synaptic plasticity. Here, we describe a new eukaryotic initiation factor 4E (eIF4E) binding protein, Neuroguidin (Ngd), and its interaction with CPEB. In the mammalian nervous system, Ngd is detected as puncta in axons and dendrites and in growth cones and filopodia. Ngd contains three motifs that resemble those present in eIF4G, 4EBP, Cup, and Maskin, all of which are eIF4E binding proteins. Ngd binds eIF4E directly, and all three motifs must be deleted to abrogate the interaction between these two proteins. In injected Xenopus oocytes, Ngd binds CPEB and, most importantly, represses translation in a cytoplasmic polyadenylation element (CPE)-dependent manner. In Xenopus embryos, Ngd is found in both neural tube and neural crest cells. The injection of morpholino-containing antisense oligonucleotides directed against ngd mRNA disrupts neural tube closure and neural crest migration; however, the wild-type phenotype is restored by the injection of a rescuing ngd mRNA. These data suggest that Ngd guides neural development by regulating the translation of CPE-containing mRNAs.

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