Premium
Protein kinase R and its cellular regulators in cancer: An active player or a surveillant?
Author(s) -
Lee Yong Sun,
Kunkeaw Nawapol,
Lee YeonSu
Publication year - 2019
Publication title -
wiley interdisciplinary reviews: rna
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.225
H-Index - 71
eISSN - 1757-7012
pISSN - 1757-7004
DOI - 10.1002/wrna.1558
Subject(s) - protein kinase r , carcinogenesis , biology , eif 2 kinase , kinase , rna interference , rna , microbiology and biotechnology , cancer , protein kinase a , cancer research , genetics , gene , mitogen activated protein kinase kinase , cyclin dependent kinase 2
Abstract 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 > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications