The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis.
Interferons (IFNs) exert antitumor activities, but the molecular mechanism underlying these effects is poorly understood. IFN-induced, double-stranded (ds) RNA-activated protein kinase (p68 kinase) has long been implicated in mediating the antiproliferative effects of IFN. In addition, recent studies suggest that p68 kinase may function as a tumor suppressor gene. In this investigation we showed that expression of p68 kinase in HeLa cells resulted in a rapid cell death characteristic of apoptosis. Rapid cell death was not observed in cells which expressed a mutant form of p68 kinase (lys296-->arg) indicating that cell death observed is the result of p68 kinase expression and activation. Moreover, infection of HeLa cells with the mutant vaccinia virus lacking E3L gene, which encodes a dsRNA binding protein that acts as an inhibitor of p68 kinase, also resulted in apoptosis. Thus, we propose that human p68 kinase functions as a tumor suppressor gene by actively participating in apoptosis.
Lee
S B
SB
Department of Biochemistry, SUNY Health Science Center at Brooklyn 11203.
Esteban
M
M
D017209:Apoptosis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014616:Vaccinia virus; D019892:eIF-2 Kinase
D011994:Recombinant Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase