Dephosphorylated Core of 2′-5′ Oligoadenylate Exerts Its Antimitogenic Effect through Mechanisms Different from the 2′-5′A-Dependent Endonuclease

Abstract

The 5′ terminally-dephosphorylated "core" of the 2′-5′ linked adenylate oligomer ppp (A2′p)₂A, termed 2-5A core [(A2′p)₂A], exerts an antimitogenic effect when added to serum-stimulated 3T3 fibroblasts. We now report that this inhibition of DNA synthesis is not an indirect effect resulting from ppp(A2′p)₂A-dependent endonuclease activation. We have shown that the 2-5A core does not activate the ppp(A2′p)₂A-dependent endonuclease when added to intact cells, based on (1) lack of the specific ribosomal RNA cleavage characteristic of the ppp(A2′p)₂A-dependent endonuclease, and (2) antimitogenic activity in a cell line (NIH-3T3, clone 1) which is defective in its ability to show activation of the ppp(A2′p)₂A-dependent endonuclease.