Initiation factor eIF2 alpha phosphorylation in stress responses and apoptosis.
The alpha subunit of polypeptide chain initiation factor eIF2 can be phosphorylated by a number of related protein kinases which are activated in response to cellular stresses. Physiological conditions which result in eIF2 alpha phosphorylation include virus infection, heat shock, iron deficiency, nutrient deprivation, changes in intracellular calcium, accumulation of unfolded or denatured proteins and the induction of apoptosis. Phosphorylated eIF2 acts as a dominant inhibitor of the guanine nucleotide exchange factor eIF2B and prevents the recycling of eIF2 between successive rounds of protein synthesis. Extensive phosphorylation of eIF2 alpha and strong inhibition of eIF2B activity can result in the downregulation of the overall rate of protein synthesis; less marked changes may lead to alterations in the selective translation of alternative open reading frames in polycistronic mRNAs, as demonstrated in yeast. These mechanisms can provide a signal transduction pathway linking eukaryotic cellular stress responses to alterations in the control of gene expression at the translational level.
Clemens
M J
MJ
Department of Biochemistry and Immunology, St George's Hospital Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK.
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase