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Evolution of eIF2α Kinases: Adapting Translational Control to Diverse Stresses

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Evolution of the Protein Synthesis Machinery and Its Regulation

Abstract

An important mechanism regulating protein synthesis involves phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF2α). In response to a range of environmental and physiological stresses, phosphorylation of eIF2α prevents this initiation factor from appropriately delivering initiator methionyl tRNA to the translation machinery. As a consequence there is lowered translation, which helps cells conserve energy and resources and better adapt to the underlying stress. During evolution, new eIF2α kinases arose by adjoining new combinations of stress-sensing regions to the kinase catalytic domain, culminating in their activation in response to different sets of stress conditions. The physiological traits of the organism and the nature of the environmental stress, along with the activating properties of each eIF2α kinase, help determine the nature and number of eIF2α kinases expressed in a given organism. This review will highlight current perspectives on the phylogenetic relationships between eIF2α kinases, the central structural and functional roles of their regulatory domains in the mechanisms regulating translational control, and how these eIF2α kinase family members evolved for optimal organism adaptation to stress.

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Acknowledgments

The authors acknowledge support by NIH grant GM049164 (RCW and MMG) and AI114851 (SR) and the Grace M. Showalter Research Trust Fund (RCW).

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Authors and Affiliations

  1. Laboratory for Host-Specific Virology, Division of Biology, Kansas State University, Manhattan, KS, 66506, USA

    Stefan Rothenburg

  2. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Millie M. Georgiadis & Ronald C. Wek

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  1. Stefan Rothenburg
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  2. Millie M. Georgiadis
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  3. Ronald C. Wek
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Correspondence to Ronald C. Wek .

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Editors and Affiliations

  1. Division of Basic Research, National Institute for Cancer, Mexico City, Distrito Federal, Mexico

    Greco Hernández

  2. Institute of Marine and Environmental Te, Univ. of Maryland Center for Environment, Baltimore, Maryland, USA

    Rosemary Jagus

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Rothenburg, S., Georgiadis, M.M., Wek, R.C. (2016). Evolution of eIF2α Kinases: Adapting Translational Control to Diverse Stresses. In: Hernández, G., Jagus, R. (eds) Evolution of the Protein Synthesis Machinery and Its Regulation. Springer, Cham. https://doi.org/10.1007/978-3-319-39468-8_11

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