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eIF2α Kinases and the Evolution of Stress Response in Eukaryotes

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Evolution of the Protein Synthesis Machinery and Its Regulation

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Abstract

The recognition of the initiation codon in mRNA is a key step of translation. In eukaryotes, this step is regulated by the activity of eIF2, the initiation factor that brings the Met-tRNAi to the small ribosomal subunit. The activity of eIF2 is regulated by phosphorylation of the α subunit at Ser51 in response to stress. This phosphorylation has two apparently opposing effects: general inhibition of protein synthesis and specific activation of stress-specific gene translation. This translation reprogramming is necessary to adapt gene expression to the new conditions, ensuring cell survival under mild stress. There are five different eIF2α kinases (GCN2, HRI, PERK, PKR and PKZ) whose phylogenetic distribution and regulatory domains reflect a growing need of higher eukaryotes to face different types of stress through specialized responses. The acquisition of stress-sensing regulatory domains endowed the primitive eIF2α kinase with the ability to respond to specific stress signals, funneling different stress responses through eIF2 activity and connecting translation activity with the cellular environment. This fact probably boosted the adaptive capacity of metazoans, especially in terms of coping with stress. In this chapter, we will discuss how different stresses have shaped the evolution of eIF2 kinases, possibly fueling the creation of the variety of eIF2α kinases known today.

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Authors and Affiliations

  1. Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049, Campus Cantoblanco, Madrid, Spain

    Juan José Berlanga, César de Haro, Miguel A. Rodríguez-Gabriel & Iván Ventoso

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  1. Juan José Berlanga
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  2. César de Haro
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  3. Miguel A. Rodríguez-Gabriel
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  4. Iván Ventoso
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Correspondence to Juan José Berlanga .

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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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Berlanga, J.J., de Haro, C., Rodríguez-Gabriel, M.A., Ventoso, I. (2016). eIF2α Kinases and the Evolution of Stress Response in Eukaryotes. 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_12

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