Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase.
The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.
Koromilas
A E
AE
Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada.
Roy
S
S
Barber
G N
GN
Katze
M G
MG
Sonenberg
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004790:Enzyme Induction; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D019892:eIF-2 Kinase
D004247:DNA; D007372:Interferons; D011494:Protein Kinases; D019892:eIF-2 Kinase