Gene

Kinase

Mitogen-activated protein kinase kinase

Cell biology

Biology

Cancer research

Protein kinase A

EIF-2 kinase

Genetics

Cyclin-dependent kinase 2

RNA interference

Protein kinase R

Carcinogenesis

Cancer

Wiley Interdisciplinary Reviews - RNA

Protein kinase R (PKR), originally known as an antiviral protein, senses various stresses as well as pathogen‐driven double‐stranded RNAs. Thereby activated PKR provokes diverse downstream events, including eIF2α phosphorylation and nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation. Consequently, PKR induces apoptosis and inflammation, both of which are highly important in cancer as much as its original antiviral role. Therefore, cellular proteins and RNAs should tightly control PKR activity. PKR and its regulators are often dysregulated in cancer and it is undoubted that such dysregulation contributes to tumorigenesis. However, PKR's precise role in cancer is still in debate, due to incomprehensible and even contradictory data. In this review, we introduce important cellular PKR regulators and discuss about their roles in cancer. Among them, we pay particular attention to nc886, a PKR repressor noncoding RNA that has been identified relatively recently, because its expression pattern in cancer can explain interesting yet obscure oncologic aspects of PKR. Based on nc886 and its regulation of PKR, we have proposed a tumor surveillance model, which reconciles contradictory data about PKR in cancer. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches &gt; Regulatory RNAs RNA Interactions with Proteins and Other Molecules &gt; Protein–RNA Interactions: Functional Implications

Protein kinase R and its cellular regulators in cancer: An active player or a surveillant?