Dinucleoside polyphosphates - friend or foe?

Despite being known for over 30 years, the functions of the dinucleoside po lyphosphates, such as diadenosine 5',5"'-P-1,P-4-tetraphosphate (Ap(4)A) an d diadenosine 5',5'''-P-1,p(3)-triphosphate (Ap(3)A), are still unclear. On the one hand, they may have important signalling functions, both inside an d outside the cell (friend), while on the other hand, they may simply be th e unavoidable by-products of certain biochemical reactions, which, if allow ed to accumulate, would be potentially toxic through their structural simil arity to ATP and other essential mononucleotides (foe). Here, the occurrenc e, synthesis, degradation, and proposed functions of these compounds are br iefly reviewed, along with some new data and recent evidence supporting rol es for Ap(3)A and Ap(4)A in the cellular decision making processes leading to proliferation, quiescence, differentiation, and apoptosis. Hypotheses ar e forwarded for the involvement of Ap(4)A in the intra-S phase DNA damage c heckpoint and for Ap(3)A and the pFhit (fragile histidine triad gene produc t) protein in tumour suppression. It is concluded that the roles of friend and foe are not incompatible, but are distinguished by the concentration ra nge of nucleotide achieved under different circumstances. (C) 2000 Elsevier Science Inc. All rights reserved.