Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function

• Published in: Nature (London) 1994-10, Vol.371 (6500), p.762-767
• Main Authors: Pause, Arnim, Belsham, Graham J, Gingras, Anne-Claude, Donzé, Olivier, Lin, Tai-An, Lawrence, John C, Sonenberg, Nahum
• Format: Article
• Language: English
• Subjects: 4E-BP1 protein; Acid Phosphatase - metabolism; Adaptor Proteins, Signal Transducing; Adipose Tissue - metabolism; Amino Acid Sequence; amino acid sequence prediction; Animals; Biochemistry; Biological and medical sciences; Carrier Proteins; cDNA; Cell Line; Cell physiology; Cloning; Cloning, Molecular; Deoxyribonucleic acid; DNA; DNA, Complementary; eIF-4E-binding protein; Escherichia coli; Eukaryotic Initiation Factor-4E; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; Insulin; Insulin - physiology; Male; man; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; nucleotide sequence; Peptide Initiation Factors - metabolism; Phosphoproteins - metabolism; Phosphorylation; placenta; Protein Binding; protein biosynthesis; Protein Biosynthesis - physiology; Protein synthesis; Proteins; Rabbits; Rats; Rats, Sprague-Dawley; RNA Caps - metabolism; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Signal transduction
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/371762a0

The cloning is described of two related human complementary DNAs encoding polypeptides that interact specifically with the translation initiation factor elF-4E, which binds to the messenger RNA 5'-cap structure. Interaction of these proteins with elF-4E inhibits translation but treatment of cells with insulin causes one of them to become hyperphosphorylated and dissociate from elF-4E, thereby relieving the translational inhibition. The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth.