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PKR, apoptosis and cancer
1Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, USA. jagus@umbi.umd.edu
Abstract:
The double-stranded (ds) RNA-regulated serine/threonine protein kinase, PKR, is an interferon-inducible enzyme of widespread occurrence in mammalian cells. PKR is activated by dsRNA via a mechanism involving autophosphorylation. Once activated, the enzyme phosphorylates the alpha-subunit of protein synthesis initiation factor eIF2, thereby inhibiting translation. Accumulating data suggest that PKR has additional substrates, and that the kinase may also regulate gene transcription and signal transduction pathways. Although PKR plays an important role in mediating the antiviral effects of interferons, PKR is also implicated in regulating cell proliferation in uninfected cells and may have a tumor suppressor function under normal conditions. Studies of human malignancies and tumor cell lines suggest that, in general, patients bearing tumors with a higher PKR content have a more favorable prognosis. However, in human breast carcinoma cells, dysregulation of PKR may be associated with the establishment or maintenance of the transformed state.
Insights
The protein kinase PKR, activated by double-stranded RNA, inhibits protein synthesis and plays a role in antiviral defense. It may also act as a tumor suppressor, with higher PKR content linked to better cancer prognosis.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- PKR is a serine/threonine protein kinase activated by double-stranded RNA (dsRNA).
- It is induced by interferons and present in most mammalian cells.
- PKR activation leads to phosphorylation of eIF2 alpha-subunit, inhibiting protein synthesis.
Purpose of the Study:
- To explore the multifaceted roles of PKR beyond its antiviral functions.
- To investigate PKR's involvement in cell proliferation and gene regulation.
- To examine the association between PKR expression and cancer prognosis.
Main Methods:
- Review of existing literature on PKR function and regulation.
- Analysis of studies investigating PKR's substrates and signaling pathways.
- Examination of data correlating PKR levels with clinical outcomes in various malignancies.
Main Results:
- PKR activation by dsRNA inhibits translation initiation.
- PKR has additional substrates and influences gene transcription and signal transduction.
- Elevated PKR levels generally correlate with a favorable prognosis in human cancers.
- Dysregulation of PKR in breast carcinoma may promote tumorigenesis.
Conclusions:
- PKR is a key regulator of protein synthesis and cellular responses to viral infection.
- PKR exhibits tumor suppressor functions, influencing cell proliferation and potentially cancer development.
- PKR levels serve as a prognostic marker in several human malignancies, though its role in breast cancer requires further investigation.