PKR, apoptosis and cancer

The double-stranded (ds) RNA-regulated serine/threonine protein kinase, PKR , is an interferon-inducible enzyme of widespread occurrence in mammalian c ells. PKR is activated by dsRNA via a mechanism involving autophosphorylati on Once activated, the enzyme phosphorylates the alpha-subunit of protein s ynthesis initiation factor eIF2, thereby inhibiting translation. Accumulati ng data suggest that PKR has additional substrates, and that the kinase may also regulate gene transcription and signal transduction pathways. Althoug h PKR plays an important role in mediating the antiviral effects of interfe rons, PKR is also implicated in regulating cell proliferation in uninfected cells and may have a tumor suppressor function under normal conditions. St udies of human malignancies and tumor cell lines suggest that, in general, patients bearing tumors with a higher PKR content have a more favorable pro gnosis. However, in human breast carcinoma cells, dysregulation of PKR may be associated with the establishment or maintenance of the transformed stat e. (C) 1999 Elsevier Science Ltd. All rights reserved.