PKR, apoptosis and cancer

Rosemary Jagus, Bhavesh Joshi, Glen N. Barber

Research output: Contribution to journalReview article

169 Scopus citations

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 α-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.

Original languageEnglish (US)
Pages (from-to)123-138
Number of pages16
JournalInternational Journal of Biochemistry and Cell Biology
Volume31
Issue number1
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Apoptosis
  • Breast cancer
  • eIF2α
  • PKR
  • Translational regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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