The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia.
The double-stranded RNA-dependent kinase, PKR, is encoded by an interferon inducible gene and is largely responsible for the anti-viral effects 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 the Tik gene, which encodes a dual-specificity kinase, is the murine homolog of PKR, the dsRNA-dependent kinase, and has undergone a rearrangement of one allele in a murine lymphocytic leukemia cell. We have cloned a cDNA that corresponds to a mutated transcript from the rearranged mPKR gene and show that while the mutated polypeptide retains its ability to dimerize and bind dsRNA, it is catalytically inactive. Although this mutated mPKR lacks apparent dominant-negative function, the net effect of reduced PKR activity in these cells may be significant.
Abraham
N
N
Ottawa Regional Cancer Center Research Laborotories, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
Jaramillo
M L
ML
Duncan
P I
PI
Méthot
N
N
Icely
P L
PL
Stojdl
D F
DF
Barber
G N
GN
Bell
J C
JC
D000483:Alleles; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D019281:Dimerization; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D007939:Leukemia L1210 / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D019892:eIF-2 Kinase / Q000235:genetics*
D015852:Eukaryotic Initiation Factor-2; D019892:eIF-2 Kinase