Agents which modify mono-ADP ribosylation can influence the differentiation of hemopoietic cells

Mono-ADP ribosylation is a post-transcriptional modification of proteins which can alter their biological properties. Particular substrates for this reaction are the GTP-binding proteins involved in the adenylate cyclase and phospholipase C second messenger pathways. Consequently, mono-ADP ribosylation may be an important element in intracellular signaling. Cholera toxin is a potent mono-ADP-ribosyl transferase, while benzylaminododecylguanine hydrochloride (BADGH) is an inhibitor of cholera toxin-induced ADP ribosylation. We have used these compounds to modulate the effects of inducers of differentiation in HL-60 cells. Cholera toxin, although unable to induce differentiation itself, synergized with inducers of both granulocytic and monocytic differentiation. In contrast, BADGH selectively inhibited the growth of undifferentiated cells. These effects imply regulatory roles for substrates for mono-ADP ribosylation both in the proliferation of undifferentiated cells and in the early stages of differentiation.