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.
Eukaryotic translation initiation factor 4E (eIF-4E), which possesses cap-binding activity, functions in the recruitment of mRNA to polysomes as part of a three-subunit complex, eIF-4F (cap-binding complex). eIF-4E is the least abundant of all translation initiation factors and a target of growth regulatory pathways. Recently, two human cDNAs encoding novel ... eIF-4E-binding proteins (4E-BPs) which function as repressors of cap-dependent translation have been cloned. Their interaction with eIF-4E is negatively regulated by phosphorylation in response to cell treatment with insulin or growth factors. The present study aimed to characterize the molecular interactions between eIF-4E and the other subunits of eIF-4F and to similarly characterize the molecular interactions between eIF-4E and the 4E-BPs. A 49-amino-acid region of eIF-4 gamma, located in the N-terminal side of the site of cleavage by Picornaviridae protease 2A, was found to be sufficient for interacting with eIF-4E. Analysis of deletion mutants in this region led to the identification of a 12-amino-acid sequence conserved between mammals and Saccharomyces cerevisiae that is critical for the interaction with eIF-4E. A similar motif is found in the amino acid sequence of the 4E-BPs, and point mutations in this motif abolish the interaction with eIF-4E. These results shed light on the mechanisms of eIF-4F assembly and on the translational regulation by insulin and growth factors.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding Sites, Carrier Proteins, Cloning, Molecular, Conserved Sequence, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factor-4F, Humans, Molecular Sequence Data, Peptide Chain Initiation, Translational, Peptide Fragments, Peptide Initiation Factors, Phosphoproteins, Protein Binding, RNA Caps, Sequence Homology, Amino Acid
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding Sites, Carrier Proteins, Cloning, Molecular, Conserved Sequence, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factor-4F, Humans, Molecular Sequence Data, Peptide Chain Initiation, Translational, Peptide Fragments, Peptide Initiation Factors, Phosphoproteins, Protein Binding, RNA Caps, Sequence Homology, Amino Acid
Mol. Cell. Biol.
Date: Sep. 01, 1995
PubMed ID: 7651417
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