Inhibition of the phosphorylation of non-histone chromosomal proteins of rat liver by cordycepin and cordycepin triphosphate.
The effects of cordycepin (3'-deoxyadenosine) and cordycepin triphosphate on phosphorylation of non-histone chromosomal proteins were assessed in isolated hepatic nuclei in vitro. Cordycepin and cordycepin triphosphate competitively inhibited phosphorylation of urea-soluble nuclear proteins with a Ki of 1.2 X 10(-3) and 8 X 10(-5) M, respectively. Isoelectric focusing of urea-soluble proteins indicated that inhibition occurred predominantly in nuclear proteins with isoelectric points of pH 4 to 7. Quaternary aminoethyl-Sephadex chromatography of extracts of nuclei incubated with cordycepin and cordycepin triphosphate also showed inhibition of phosphorylation of non-histone chromosomal proteins with similar isoelectric points, although greater resolution of proteins with isoelectric points of pH 6 to 7 was achieved. RNA polymerase I and II were not affected by cordycepin and cordycepin triphosphate after quaternary aminoethyl-Sephadex chromatography of nuclear extracts incubated with either agent. However, RNA polymerase I and II in isolated nuclei were competitively inhibited by cordycepin triphosphate but not by cordycepin. These results suggest that cordycepin triphosphate, and perhaps cordycepin too, may affect transcription via interference with the phosphorylation of non-histone chromosomal proteins.
D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D012318:RNA Polymerase I / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D002868:Chromosomal Proteins, Non-Histone; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D012319:RNA Polymerase II; D012318:RNA Polymerase I