Role of interferon and 2',5'-oligoadenylate synthetase in erythroid differentiation of Friend leukemia cells. Studies with interferon-sensitive and -resistant variants.
It has been suggested that the interferon (IFN)-induced 2',5'-oligoadenylate (2-5A) synthetase, which polymerizes ATP into a series of 2',5'-linked oligomers with the general formula pppA(2'p5'A)n, plays a general role in cell growth and terminal differentiation. For instance, an increase in 2-5A synthetase activity has been described during dimethyl sulfoxide (Me2SO)-induced erythroid differentiation of Friend leukemia cells (FLC). 2-5A synthetase has been measured in two Friend leukemia cell sublines by various techniques including a radioimmunoassay of its products which would detect 10(-16) mol of 2-5A cores. Although cells of both sublines fully differentiate (as measured by benzidine staining), only in one subline was there an increase in 2-5A synthetase activity upon treatment with Me2SO. Hexamethylenebisacetamide, another potent agent of differentiation in this system, did not increase 2-5A synthetase activity in either of these two sublines. An IFN-resistant FLC variant differentiated normally upon treatment with Me2SO or hexamethylenebisacetamide while it was noninducible for 2-5A synthetase activity by exogenous IFN or by the inducers themselves. A similar situation has been observed with regard to the level of phosphorylation of the IFN-induced Mr = 67,000 protein band. In addition, treatment of IFN-sensitive and resistant FLC sublines with mouse alpha beta IFN antiserum did not affect differentiation. Even though we have duplicated previous findings on the increase of 2-5A synthetase activity in Me2SO-induced FLC, the lack of any such increase with other inducers or other sublines indicates that there is no causal relationship between the enzyme activation and FLC differentiation.
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004790:Enzyme Induction; D007370:Interferon Type I / Q000494:pharmacology*; D007739:L Cells / Q000276:immunology; D007942:Leukemia, Experimental / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D009522:Newcastle disease virus / Q000276:immunology; D011494:Protein Kinases / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000081:Acetamides; D007370:Interferon Type I; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase; C014026:hexamethylene bisacetamide