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 polysome s as part of a three-subunit complex, eIF-4F (cap-binding complex), eI F-4E is the least abundant of all translation initiation factors and a target of growth regulatory pathways, Recently, two human cDNAs encod ing novel eIF-4E-binding proteins (4E-BPs) which function as repressor s of cap-dependent translation have been cloned, Their interaction wit h eIF-4E is negatively regulated by phosphorylation in response to cel l 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 interac tions between eIF-4E and the 4E-BPs. A 49-amino-acid region of eIF-4 g amma, located in the N-terminal side of the site of cleavage by Picorn aviridae protease 2A, was found to be sufficient for interacting with eIF-4E, Analysis of deletion mutants in this region led to the identif ication of a 12-amino-acid sequence conserved between mammals and Sacc haromyces cerevisiae that is critical for the interaction with eIF-4E. A similar motif is found in the amino acid sequence of the 4E-BPs, an d point mutations in this motif abolish the interaction with eIF-4E. T hese results shed light on the mechanisms of eIF-4F assembly and on th e translational regulation by insulin and growth factors.