tailieunhanh - Insulin Action and Its Disturbances in Disease - part 3

Khởi dịch mRNA thành protein bắt đầu hình thành các nắp guanine 7methyl vào cuối 5 chính của RNA. Một số protein liên quan cap bao gồm cả yếu tố khởi đầu eukaryotic 4E (eIF-4E), eIF-4G và phosphoryl hóa protein nhiệt ổn định acid (PHAS-1) bị ảnh hưởng bởi insulin | 108 THE EFFECT OF INSULIN ON PROTEIN METABOLISM mechanisms whereby insulin selectively affects mRNA stability have not been well defined. Initiation of mRNA translation into protein begins with formation of the 7-methyl guanine cap at the 5-prime end of the RNA. A number of cap-associated proteins including eukaryotic initiation factor 4E eIF-4E eIF-4G and phosphorylated heat-acid-stable protein PHAS-1 are influenced by insulin. PHAS-1 binds to the eIF-4E cap binding protein insulin enhances phosphorylation of PHAS-1 and favours dissociation of eIF-4E and This allows for binding of eIF-4E to eIF-4G and hence favours association with the 40S ribosomal subunit and translation 16 Also important in the binding of the 40S ribosomal subunit is eIF-2 and the binding of this initiation factor is dependent on its association with GTP. Controlling the recycling of the GTP GDP-bound state of eIF-2 is eIF-2B. Insulin increases the activity of eIF-2B and favours the GTP-bound active state of eIF-2 which in turn enhances translation 17 Protein elongation depends on the action of multiple elongation factors. Among these are elongation factor 2 eEF-2 . This factor is important for movement of the ribosomal complex along the mRNA and for the migration of the amino acyl-tRNA from the acceptor site to the peptidyl site of the Insulin enhances eEF-2 activity by reducing its phosphorylation via inhibition of its A comprehensive description of the molecular mechanisms of insulin s effect on translation is available in review The abundance of ribosomes and RNA content in part determines the cellular capacity to synthesize Ribosomes are made up of approximately 80 proteins and 4 ribosomal RNA rRNA species. Production and assembly of ribosomes takes place in the nuclei. In chick embryo fibroblasts insulin has been shown to induce a fourfold increase in the synthesis of ribosomal Similar findings have