Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors.

摘要: We have examined the effects of widely used stress-inducing agents on protein synthesis and regulatory components translational machinery. The three stresses chosen, arsenite, hydrogen peroxide sorbitol, exert their in quite different ways. Nonetheless, all rapidly (? 30 min) caused a profound inhibition synthesis. In each case this was accompanied by dephosphorylation eukaryotic initiation factor (eIF) 4E-binding 1 (4E-BP1) increased binding repressor to eIF4E. Binding 4E-BP1 eIF4E correlated with loss eIF4F complexes. Sorbitol 70-kDa ribosomal S6 kinase, while arsenite activated it. phosphorylation elongation 2 also differed: oxidative stress elicited marked increase eEF2 phosphorylation, which is expected contribute translation, other did not effect. Although proteins (4E-BP1, p70 kinase eEF2) can be regulated through mammalian target rapamycin (mTOR), our data imply that do interfere mTOR function but act ways these proteins. All activate p38 MAP pathway we were able exclude role for 4E-BP1. Our reveal agents, are study stress-signalling cells, multiple complex inhibitory