Diadenosine 5', 5"'-P1,P4-tetraphosphate stimulates processing of adp-ribosylated poly(ADP-ribose) polymerase.
The effect of diadenosine 5', 5"'-P1,P4-tetraphosphate (Ap4A) on the time course and acceptors of poly(ADP-ribose) synthesis was studied in undamaged and N-methyl-N'-nitro-N-nitrosoguanidine-treated human lymphocytes. Analysis of protein acceptors of poly(ADP-ribose) revealed that treatment with Ap4A stimulated ADP-ribosylation of bands at molecular weights of 96,000, 79,000, and 62,000. Pulse-chase studies showed that these bands were produced as a result of an effect of Ap4A on the processing of ADP-ribosylated proteins rather than on the synthesis of newly ADP-ribosylated proteins. By incubating permeabilized cells in the absence or presence of Ap4A and purified poly(ADP-ribose) polymerase auto-ADP-ribosylated with [32P]NAD+, we showed that the Mr = 96,000, 79,000, and 62,000 bands were derivatives of the prelabeled enzyme. Our results indicate that normal human lymphocytes process auto-ADP-ribosylated poly(ADP-ribose) polymerase to specific lower molecular weight products and that this processing is stimulated by Ap4A.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D015226:Dinucleoside Phosphates; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008970:Molecular Weight; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D008769:Methylnitronitrosoguanidine; C020733:diadenosine tetraphosphate; D011065:Poly(ADP-ribose) Polymerases; D009244:NAD+ Nucleosidase