A historical overview of protein kinase PKR: from its discovery and mechanism of action to its clinical and therapeutic implications

Abstract

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells. PKR plays an active part in the cellular response to numerous types of stress, with a critical role in the host's interferon-induced antiviral defence mechanisms. PKR has been extensively studied and documented for its relevance as a cell growth regulator, and more recently analysed in connection with metabolism, inflammatory processes, cancer, and neurodegenerative diseases. The present review will summarise, in chronological order, the state of the knowledge about this kinase as well as the contributions we have done at the National Centre of Biotechnology regarding the regulation and mechanisms of action of PKR. Specific mention will be made of the studies that the author leads at the University Hospital Complex of Granada, showing the importance that PKR has as a target of both conventional chemotherapeutics and novel drugs, and its potential as a biomarker and therapeutic target in various pathologies.