Activation of the IFN-inducible enzyme RNase L causes apoptosis of animal cells.
The interferon (IFN)-induced enzyme RNase L produced by a recombinant vaccinia virus (VV) causes death of mammalian cells with morphological and biochemical characteristics of apoptosis. Coexpression of 2-5A-synthetase enhances apoptosis induced by RNase L Activation of endogenous RNase L by infection with a VV ts mutant (ts22) or with wild-type virus in the presence of the antipoxvirus drug isatin-beta-thiosemicarbazone, a treatment known to significantly increase the amount of double-stranded RNA late during infection, also causes pronounced apoptosis of infected cells. The effects observed with recombinant virus-derived RNase L or with the endogenous enzyme are specific, since apoptosis also occurs in cells derived from mice lacking the IFN-induced protein kinase (PKR). The apoptosis antagonist Bcl-2 prevents induction of cell death by RNase L activation. Apoptosis of mammalian cells by RNase L activation could be a mechanism mediating anticellular actions of IFN.
Díaz-Guerra
M
M
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Rivas
C
C
Esteban
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004722:Endoribonucleases / Q000096:biosynthesis / Q000378:metabolism*; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D011995:Recombination, Genetic; D014616:Vaccinia virus / Q000201:enzymology / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D007372:Interferons; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease