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Tumor progression and the different faces of the PERK kinase

Oncogene volume 35, pages 1207–1215 (2016)Cite this article

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Abstract

The serine/threonine endoplasmic reticulum (ER) kinase, protein kinase R (PKR)-like ER kinase (PERK), is a pro-adaptive protein kinase whose activity is regulated indirectly by protein misfolding within the ER. As the oxidative folding environment in the ER is sensitive to a variety of cellular stresses, many of which occur during neoplastic transformation and in the tumor microenvironment, there has been considerable interest in defining whether PERK positively contributes to tumor progression and whether it represents a significant therapeutic target. Herein, we review the current knowledge of PERK-dependent signaling pathways, the contribution of downstream substrates including recently characterized new PERK substrates transcription factors Forkhead box O protein and diacyglycerol a lipid signaling second messenger, and efforts to develop small molecule PERK inhibitors.

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Acknowledgements

This work was supported by National Institutes of Health grant CA104838 (JAD); Polish National Science Centre (NCN) ‘HARMONIA 5’ grant no. 2013/10/M/N21/00280.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

    D Pytel & J A Diehl

  2. Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Hallera 1, Lodz, Poland

    I Majsterek

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  1. D Pytel
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Pytel, D., Majsterek, I. & Diehl, J. Tumor progression and the different faces of the PERK kinase. Oncogene 35, 1207–1215 (2016). https://doi.org/10.1038/onc.2015.178

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