Stimulation of phosphorylation of a nuclear protein (NP-34) in cultured Alzheimer's disease (AD) fibroblasts by interferon response element and other double-stranded oligonucleotides.
The interferon stimulated responsive elements (IRE), which correspond to nucleotide sequences between -103 and -85 (IRE18) and between -103 and -61 (IRE42), of the human 2',5'-oligoadenylate (2-5A) synthetase gene, were found to stimulate the phosphorylation of a number of proteins when added to nuclear extracts prepared from cultured AD fibroblasts; the most significant increase being a 34-kD protein, NP-34. Such an IRE-stimulated phosphorylation was less pronounced in normal fibroblast extracts. Other oligomers tested for IRE-like activity were found to be differentially effective. The relative activity of oligomers was correlated with their ability to be organized into an IRE42-like conformation. The IRE-dependent stimulation of the phosphorylation of nuclear proteins is most likely associated with the activation of a double-stranded DNA-dependent protein kinase (DNA-PK) since the IRE-stimulated phosphorylation of NP-34 was enhanced by the addition of purified HeLa DNA-PK, but reduced by a DNA-PK-specific monoclonal antibody.
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Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
Maturana
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Wu
J M
JM
D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D005347:Fibroblasts; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011067:Poly dA-dT / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid
D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011067:Poly dA-dT; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase