Induction of human HL-60 leukemic cell differentiation by immune interferon is accompanied by an increase in NADase activity and by a decrease in DNA-binding proteins.
The effects of highly purified human immune interferon (IFN-gamma) on the differentiation of human promyelocytic HL-60 leukemic cells have been studied. The addition of 100 units/ml interferon to HL-60 cells for 5 days results in morphological changes characteristic of macrophages. At the biochemical level, there is a 3-fold increase in the specific activity of the enzyme NADase. Kinetic analysis shows that IFN-gamma causes an increase in the Vmax of NADase without affecting the apparent Km. Pulse labeling experiments with [35S] methionine show a marked change in the de novo synthesis of several proteins in the course of interferon treatment. Chromatography on DNA-agarose show that after treatment with interferon for 24 or 48 h, there is a 60-70% decrease in newly synthesized proteins which bind DNA-agarose and can be subsequently displaced from the column with 2% SDS containing buffer (from 7.7-8.7% bound in control cell extracts to 2.6-3.1% bound in interferon treated cell extract).
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D007371:Interferon-gamma; D009244:NAD+ Nucleosidase; D013755:Tetradecanoylphorbol Acetate