Role of interferon and 2‘,5‘-oligoadenylate synthetase in erythroid differentiation of Friend leukemia cells. Studies with interferon-sensitive and -resistant variants

• Published in: The Journal of biological chemistry Vol. 259; no. 5; pp. 3261 - 3265
• Main Authors: Mechti, N, Affabris, E, Romeo, G, Lebleu, B, Rossi, G B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.03.1984; American Society for Biochemistry and Molecular Biology
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; Acetamides - pharmacology; Animals; Cell Differentiation - drug effects; Cell Line; Enzyme Induction; Interferon Type I - pharmacology; L Cells - immunology; Leukemia, Experimental - enzymology; Leukemia, Experimental - physiopathology; Life Sciences; Mice; Newcastle disease virus - immunology; Protein Kinases - metabolism; Vesicular stomatitis Indiana virus - immunology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)43289-3

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.