Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase

摘要: Abstract RNA-dependent protein kinase is a M(r) 68,000 in human cells (p68 kinase) or 65,000 murine (p65 kinase). p65/p68 serine/threonine induced by interferon treatment and generally activated double-stranded RNAs. Once activated, the known function of this inhibition synthesis through phosphorylation eukaryotic initiation factor 2. Here we have investigated potential for tumorigenicity mice NIH 3T3 clones expressing p68 kinase, either wild-type mutant inactive with single amino acid substitution invariant lysine-296 catalytic domain II. Expression was correlated malignant transformation phenotype, giving rise to production large tumors at least 1 cm diameter within 7-12 days all inoculated mice. In contrast, no tumor growth observed several weeks cell recombinant only endogenous p65 analogue kinase. These results suggest that functional (recently called PKR), still undefined mechanism, may also act as suppressor. Consequently, one pathways which inhibits might be its capacity induce enhanced expression