From activator to suppressor: PACT is joining the company of PKR negative regulators
- Francisco M. Acosta1,2 and
- Christian K. Pfaller1,2,3
- 1Virology and Gene Therapy Track, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota 55901, USA
- 2Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55901, USA
- 3Division of Veterinary Medicine, Paul-Ehrlich-Institute, Langen 63225, Germany
- Corresponding author: pfaller.christian{at}mayo.edu
This extract was created in the absence of an abstract.
In this issue of RNA, Young et al. identify a new regulatory role of the protein activator of the interferon-induced protein kinase (PACT, PRKRA gene) on the activation of protein kinase R (PKR) (Young et al. 2025). PKR is one of four cellular stress-activated kinases inducing global protein translation shutdown through phosphorylation of their natural substrate, the eukaryotic initiation factor 2-α (eIF2α). PKR activation occurs through binding to double-stranded RNA (dsRNA), a hallmark of many viral infections. As such, PKR is an integral part of the cell-intrinsic innate immune response system against viral pathogens (Pfaller et al. 2011). However, tight regulation of PKR activation is essential for maintaining cell viability and health. A large body of evidence published in the past decade has revealed that endogenous dsRNA structures can activate PKR as well as the dsRNA sensors melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid–inducible gene I (RIG-I), thereby …
