Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras.
Activation of 2-5A-dependent ribonuclease by 5'-phosphorylated, 2',5'-linked oligoadenylates, known as 2-5A, is one pathway of interferon action. Unaided uptake into HeLa cells of 2-5A linked to an antisense oligonucleotide resulted in the selective ablation of messenger RNA for the double-stranded RNA (dsRNA)-dependent protein kinase PKR. Similarly, purified, recombinant human 2-5A-dependent ribonuclease was induced to selectively cleave PKR messenger RNA. Cells depleted of PKR activity were unresponsive to activation of nuclear factor-kappa B (NF-kappa B) by the dsRNA poly(I):poly(C), which provides direct evidence that PKR is a transducer for the dsRNA signaling of NF-kappa B.
Maran
A
A
Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.
Maitra
R K
RK
Kumar
A
A
Dong
B
B
Xiao
W
W
Li
G
G
Williams
B R
BR
Torrence
P F
PF
Silverman
R H
RH
D000227:Adenine Nucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D001483:Base Sequence; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D019892:eIF-2 Kinase
D000227:Adenine Nucleotides; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D012333:RNA, Messenger; C023505:2',5'-oligoadenylate; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease