Phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by kinases, such as GCN2, regulates protein translation, which is central for determining cell fate in response to environmental stresses. Unlike single-cell eukaryotes, which lack a specific eIF2α phosphatase, mammals have two eIF2α phosphatases, PPP1R15A and PPP1R15B, the combined deletion of which leads to early embryonic lethality; because of the severity of this phenotype, however, its mechanism has been difficult to study. On page 1406, Stefan Marciniak and colleagues set out to characterise a putative PPP1R15 orthologue, and use Drosophila melanogaster to dissect its role during development. The authors show that Drosophila PPP1R15 is widely expressed during embryogenesis, and is functionally homologous to mammalian PPP1R15B. Although not transcriptionally regulated, the expression of Drosophila PPP1R15 is controlled by the presence of upstream open reading frames in its 5′UTR, which enables its induction in response to phosphorylation of eIF2α. Furthermore, the authors find that Drosophila PPP1R15 expression is necessary for embryonic and larval development, and that this is to oppose the inhibitory effects of GCN2 on anabolic growth. This work represents the first description of a non-mammalian eIF2α phosphatase, and suggests that its evolution occurred to enable anabolic growth in metazoans.
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IN THIS ISSUE| 15 March 2013
PPP1R15 and GCN2 in development
Online Issn: 1477-9137
Print Issn: 0021-9533
© 2013. Published by The Company of Biologists Ltd
J Cell Sci (2013) 126 (6): e0601.
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PPP1R15 and GCN2 in development. J Cell Sci 15 March 2013; 126 (6): e0601. doi:
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