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RESEARCH PRODUCT

Homologies Between Different Forms of 2-5A Synthetases

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(2′-5′) Oligoadenylate synthetases (2-5A synthetases; EC 2.7.7.19) are present in mammalian cells and tissues and synthesize from ATP a series of oligomers termed 2-5A [general formula: ppp(A2′p)nA; with 1 ≤ n < 18 and usually 1 ≤ n < 6] (Hovanessian 1991). For full enzymic activity of the 2-5A synthetases, binding of double-stranded RNA is required (Sen 1982). Three principal 2-5A synthetase isoenzymes have been described with Mr’s of 40–46, 69, and 100 kDa (Chebath et al. 1987; Hovanessian et al. 1987, 1988). In the following they are classified as 2-5A synthetase I [Mr 40–46 000], II [Mr 69 000] and III [Mr 100 000]. All three isoforms are induced in cells by interferon (Cohen et al. 1988; Rutherford et al. 1988). 2-5A synthetases I and II are present in both the nucleus and the mitochondria as well as in the rough/smooth microsomal fraction, while 2-5A synthetase III is associated with the rough microsomal fraction only (Hovanessian et al. 1987). The enzymic product, 2-5A, functions as an activator of the endoribonuclease L. 2-5A is rapidly degraded either by the relatively unspecific phosphodiesterase (Schmidt et al. 1979; Johnston and Hearl 1987) or the specific 2′,3′-exoribonuclease (Muller et al. 1980; Schroder et al. 1980, 1984).