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Updated: May 3, 2026
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
The impact of PKR activation: from neurodegeneration to cancer
Juan A Marchal1, Gabriel J Lopez, Macarena Peran
11University Hospital Virgen de las Nieves, Azpitarte sn., Granada E-18012, Spain. mangelgarcia@ugr.es.
Abstract:
An inverse association between cancer and neurodegeneration is plausible because these biological processes share several genes and signaling pathways. Whereas uncontrolled cell proliferation and decreased apoptotic cell death governs cancer, excessive apoptosis contributes to neurodegeneration. Protein kinase R (PKR), an interferon-inducible double-stranded RNA protein kinase, is involved in both diseases. PKR activation blocks global protein synthesis through eIF2α phosphorylation, leading to cell death in response to a variety of cellular stresses. However, PKR also has the dual role of activating the nuclear factor κ-B pathway, promoting cell proliferation. Whereas PKR is recognized for its negative effects on neurodegenerative diseases, in part, inducing high level of apoptosis, the role of PKR activation in cancer remains controversial. In general, PKR is considered to have a tumor suppressor function, and some clinical data show a correlation between suppressed or inactivated PKR and a poor prognosis for several cancers. However, other studies show high PKR expression and activation levels in various cancers, suggesting that PKR might contribute to neoplastic progression. Understanding the cellular factors and signals involved in the regulation of PKR in these age-related diseases is relevant and may have important clinical implications. The present review highlights the current knowledge on the role of PKR in neurodegeneration and cancer, with special emphasis on its regulation and clinical implications.
Insights
Protein kinase R (PKR) plays a dual role in age-related diseases. While inhibiting neurodegeneration by promoting apoptosis, its role in cancer, whether tumor-suppressive or oncogenic, remains complex and warrants further investigation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- Cancer and neurodegeneration share genetic and signaling pathways, but have opposing cellular mechanisms (proliferation vs. apoptosis).
- Protein kinase R (PKR) is an interferon-inducible enzyme implicated in both cellular stress responses and disease pathways.
- PKR's role in neurodegeneration is generally considered protective, while its function in cancer is debated.
Purpose of the Study:
- To review the current understanding of Protein kinase R (PKR) involvement in neurodegeneration and cancer.
- To emphasize the regulatory mechanisms of PKR in these age-related diseases.
- To discuss the clinical implications of PKR's dual role.
Main Methods:
- Literature review of studies on PKR in cancer and neurodegeneration.
- Analysis of signaling pathways involving PKR, including eIF2α phosphorylation and NF-κB activation.
- Examination of clinical data correlating PKR status with disease prognosis.
Main Results:
- PKR activation can induce apoptosis, contributing to neuroprotection, but also activate pathways promoting cell proliferation.
- Evidence suggests PKR may act as a tumor suppressor, with inactivated PKR linked to poor cancer prognosis.
- Conversely, some studies indicate elevated PKR expression and activation in cancers, suggesting a pro-neoplastic role.
Conclusions:
- The precise role of PKR in cancer remains controversial, with evidence supporting both tumor-suppressive and oncogenic functions.
- Understanding PKR regulation is crucial for deciphering its complex involvement in age-related diseases.
- Further research into PKR's mechanisms and clinical implications may offer therapeutic strategies for neurodegeneration and cancer.
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