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An Overview of Methods for Detecting eIF2α Phosphorylation and the Integrated Stress Response

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The Integrated Stress Response

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2428))

Abstract

Phosphorylation of the translation initiation factor eIF2α is an adaptive signaling event that is essential for cell and organismal survival from yeast to humans. It is central to the integrated stress response (ISR) that maintains cellular homeostasis in the face of threats ranging from viral infection, amino acid, oxygen, and heme deprivation to the accumulation of misfolded proteins in the endoplasmic reticulum. Phosphorylation of eIF2α has broad physiological, pathological, and therapeutic relevance. However, despite more than two decades of research and growing pharmacological interest, phosphorylation of eIF2α remains difficult to detect and quantify, because of its transient nature and because substoichiometric amounts of this modification are sufficient to profoundly reshape cellular physiology. This review aims to provide a roadmap for facilitating a robust evaluation of eIF2α phosphorylation and its downstream consequences in cells and organisms.

Agnieszka Krzyzosiak and Aleksandra P. Pitera should be considered equal first authors.

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Acknowledgments

We are grateful to the Bertolotti lab members for discussions and comments, D. Alessi and M. Goedert for comments on the manuscript, and J. Westmoreland for the illustration. A.K. was supported by the European Molecular Biology Organization (EMBO, ALTF 1171-2013) and Human Frontier Science Program (LT000888/2014-L). A.P.P. and A.B. are supported by the Medical Research Council (MC_U105185860).

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  1. MRC Laboratory of Molecular Biology, Cambridge, UK

    Agnieszka Krzyzosiak, Aleksandra P. Pitera & Anne Bertolotti

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  1. Agnieszka Krzyzosiak
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  3. Anne Bertolotti
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Correspondence to Anne Bertolotti .

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  1. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    Daniel Matějů

  2. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    Jeffrey A. Chao

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Krzyzosiak, A., Pitera, A.P., Bertolotti, A. (2022). An Overview of Methods for Detecting eIF2α Phosphorylation and the Integrated Stress Response. In: Matějů, D., Chao, J.A. (eds) The Integrated Stress Response. Methods in Molecular Biology, vol 2428. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1975-9_1

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