eIF2α phosphorylation and the regulation of translation
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We discuss novel insight into the role and consequences of the phosphorylation of the translation initiation factor eIF2α in the context of stress responses and cell-cycle regulation. eIF2α is centrally located to regulate translation and its phosphorylation in response to different environmental challenges is one of the best characterized stress-response pathways. In addition to its role in stress management, eIF2α phosphorylation is also linked to cell-cycle progression and memory consolidation in the nervous system. The best known consequences of eIF2α phosphorylation are downregulation of global translation and stimulation of translation of some mRNAs. However, recent evidence shows that (i) eIF2α phosphorylation is not always required for the downregulation of global translation after exposure to stress and (ii) eIF2α phosphorylation does not necessarily lead to the downregulation of global translation. These results suggest that the textbook view of eIF2α phosphorylation needs to be revised and that there must be additional regulatory mechanisms at play.
KeywordseIF2α phosphorylation Stress response Cell cycle Selective translation Global translation
We thank Silje Anda for comments on the manuscript, past and present group members for helpful discussions and the Norwegian Research Council, the Norwegian Cancer Society, the South-Eastern Norwegian Health Authority, the Simon Fougner Hartmanns Familiefond and Radiumhospitalets Legater for funding.
- Dever TE, Chen JJ, Barber GN, Cigan AM, Feng L, Donahue TF, London IM, Katze MG, Hinnebusch AG (1993) Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast. Proc Natl Acad Sci USA 90:4616–4620CrossRefGoogle Scholar
- Elliott SG, McLaughlin CS (1979) Synthesis and modification of proteins during the cell cycle of the yeast Saccharomyces cerevisiae. J Bacteriol 137:1185–1190Google Scholar
- Gismondi A, Caldarola S, Lisi G, Juli G, Chellini L, Iadevaia V, Proud CG, Loreni F (2014) Ribosomal stress activates eEF2 K–eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes. Nucleic Acids Res 42:12668–12680CrossRefGoogle Scholar
- Imami K, Milek M, Bogdanow B, Yasuda T, Kastelic N, Zauber H, Ishihama Y, Landthaler M, Selbach M (2018) Phosphorylation of the ribosomal protein RPL12/uL11 affects translation during mitosis. Mol Cell 72(84–98):e89Google Scholar
- Zhan K, Vattem KM, Bauer BN, Dever TE, Chen JJ, Wek RC (2002) Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for resistance to environmental stresses. Mol Cell Biol 22:7134–7146CrossRefGoogle Scholar