Bulk calf thymus histone proteins, when included in reaction mixtures, inhibit activation of partially purified double-stranded (ds) RNA-dependent protein kinase, and are themselves only poorly phosphorylated. This inhibition of enzyme activation could be overcome by preincubating enzyme with dsRNA, in the absence of ATP, or by increasing the dsRNA concentration to 100 μg/ml. Under these conditions histone proteins were actively phosphorylated. In addition, histone proteins could reverse the nonactivating effects of preincubating enzyme with a high concentration of dsRNA. We demonstrate that histone proteins bind specifically to dsRNA. These results suggest that inhibition of kinase activation by histone is due to competition for binding to available dsRNA. Several virus-encoded inhibitors of the interferon-induced protein kinase are likely dsRNA-binding proteins, which may function in a manner analogous to histone proteins.
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