THE MURINE PKR TUMOR-SUPPRESSOR GENE IS REARRANGED IN A LYMPHOCYTIC-LEUKEMIA

The double-stranded RNA-dependent kinase, PKR, is encoded by an interf eron inducible gene and is largely responsible for the anti-viral effe cts of this cytokine. Recent studies have shown that PKR may also play a role in the regulation of normal cellular growth. Although numerous examples of viral strategies for inactivation of PKR exist, there is no evidence of PKR inactivation in tumors. We demonstrate here that th e Tik gene, which encodes a dual-specificity kinase, is the murine hom olog of PKR, the dsRNA-dependent kinase, and has undergone a rearrange ment of one allele in a murine lymphocytic leukemia cell. We have clon ed a cDNA that corresponds to a mutated transcript from the rearranged mPKR gene and show that while the mutated polypeptide retains its abi lity to dimerize and bind dsRNA, it is catalytically inactive. Althoug h this mutated mPKR lacks apparent dominant-negative function, the net effect of reduced PKR activity in these cells may be significant. (C) 1998 Academic Press.