The dsRNA-dependent protein kinase, PKR and cell death

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

PKR has been shown to potentially regulate cell death in response to a number of stimuli such as dsRNA, and may even be activated following direct interaction with other proteins. What is less clear is how PKR may mediate these effects. While some data indicate that PKR can facilitate cell death through eIF2α and the regulation of translation, other data indicate that this may not be sufficient on its own to trigger apoptosis. Almost certainly a combination of other stress-related events would need to occur to condemn the cell to die. Presently, it is clear that PKR is important in preventing virus translation, through eIF2α phosphorylation, following infection of the cell. This event would allow time for IFN to be produced, to fortify an antiviral state. However, it is also extremely likely that PKR functions to regulate pathways other than those involving eIF2 that may similarly facilitate host defense against virus infection or which govern cell death. This could involve signaling mechanisms involving the FADD, NF-κB or the p38, MAPK stress kinase pathways. Elucidating the exact mechanisms of PKR-associated cell death remains an important issue since this kinase plays a key role in antiviral host defense and perhaps tumorigenesis. In addition, recent studies show that PKR may play a role in neurogenerative diseases. The potential value of understanding how PKR may regulate cell growth and apoptosis may thus provide therapeutic opportunities that could be exploited in strategies designed to combat viral, malignant and neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)563-570
Number of pages8
JournalCell Death and Differentiation
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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