Roles of protein kinase R in cancer: Potential as a therapeutic target

Cancer Science
Takao WatanabeYoichi Hiasa

Abstract

Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune antiviral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor as a result of its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant disease, such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus (HCV) is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of tr...Continue Reading

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Citations

Mar 21, 2020·Advanced Science·Abdullah F U H SaeedSongying Ouyang
Dec 15, 2018·Physiological Reports·Rudy J ValentineHyeyoon Eo
Jul 25, 2020·Journal of Hematology & Oncology·Chaeuk ChungEun-Kyeong Jo
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Aug 24, 2020·Current Problems in Cancer·Nasser Hashemi GoradelBabak Negahdari
Feb 11, 2021·International Journal of Molecular Sciences·Shu-Chun ChangJeak Ling Ding
Mar 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Brittany L CarpenterPeter A Jones
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Jul 27, 2021·Frontiers in Immunology·Robin Smyth, Jim Sun
Mar 17, 2020·Biochemistry·Cassie M Zerbe, James L Cole

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Methods Mentioned

BETA
xenograft

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