The role of 2'-5' oligoadenylate-activated ribonuclease L in apoptosis.
Apoptosis of viral infected cells appears to be one defense strategy to limit viral infection. Interferon can also confer viral resistance by the induction of the 2-5A system comprised of 2'-5' oligoadenylate synthetase (OAS), and RNase L. Since rRNA is degraded upon activation of RNase L and during apoptosis and since both of these processes serve antiviral functions, we examined the role RNase L may play in cell death. Inhibition of RNase L activity, by transfection with a dominant negative mutant, blocked staurosporine-induced apoptosis of NIH3T3 cells and SV40-transformed BALB/c cells. In addition, K562 cell lines expressing inactive RNase L were more resistant to apoptosis induced by decreased glutathione levels. Hydrogen peroxide-induced death of NIH3T3 cells did not occur by apoptosis and was not dependent upon active RNAse L. Apoptosis regulatory proteins of the Bcl-2 family did not exhibit altered expression levels in the absence of RNase L activity. RNase L is required for certain pathways of cell death and may help mediate viral-induced apoptosis.
Castelli
J C
JC
Biochemistry Section, Surgical Neurology Branch, NINDS, NIH, Bethesda, Maryland 20892-1414, USA.
Hassel
B A
BA
Maran
A
A
Paranjape
J
J
Hewitt
J A
JA
Li
X L
XL
Hsu
Y T
YT
Silverman
R H
RH
Youle
R J
RJ
D016475:3T3 Cells; D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D019254:Genes, bcl-2; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020014:K562 Cells; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D009843:Oligoribonucleotides / Q000378:metabolism*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000227:Adenine Nucleotides; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D004791:Enzyme Inhibitors; D008298:Maleates; D009843:Oligoribonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C023505:2',5'-oligoadenylate; D006861:Hydrogen Peroxide; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; C014476:diethyl maleate; D019311:Staurosporine