ELEVATION OF INTERFERON BETA-INDUCIBLE PROTEINS IN ATAXIA-TELANGIECTASIA CELLS

The recently cloned ATM gene has been shown to hear considerable homol ogy to phosphatidylinositol 3 kinases and, therefore, its product may function in signal transduction. In this study, we report constitutive ly elevated levels of two IFN-beta-inducible proteins, ubiquitin cross -reactive protein (UCRP), and low molecular weight protein (LMP2), in human fibroblasts with the inherited disease ataxia telangiectasia (AT ), Using immunoblotting, it was found that a M(r) 15,000 band represen ting free UCRP was hardly detectable in normal cells, while it was the predominant band in AT cells. Similarly, the expression of a M(r) 23, 000 protein, LMP2, was found to be higher in AT cells than in normal c ells. Culturing three successive passages of the AT cell line in the p resence of different concentrations of neutralizing antibodies against IFN-beta caused partial and complete reduction, respectively, of the free UCRP and LMP2 signals to normal levels. These results indicate th at UCRP and LMP2 pools may be basally elevated in AT cells due to cons titutive activation of the IFN-beta induction pathway and are in keepi ng with the recently reported constitutive activation of the NF-kappa B transcriptional activator in AT cells.