Dinucleoside polyphosphates—friend or foe?
2000; Elsevier BV; Volume: 87; Issue: 2-3 Linguagem: Inglês
10.1016/s0163-7258(00)00041-3
ISSN1879-016X
Autores Tópico(s)Calcium signaling and nucleotide metabolism
ResumoDespite being known for over 30 years, the functions of the dinucleoside polyphosphates, such as diadenosine 5′,5′′′-P1,P4-tetraphosphate (Ap4A) and diadenosine 5′,5′′′-P1,P3-triphosphate (Ap3A), are still unclear. On the one hand, they may have important signalling functions, both inside and outside the cell (friend), while on the other hand, they may simply be the unavoidable by-products of certain biochemical reactions, which, if allowed to accumulate, would be potentially toxic through their structural similarity to ATP and other essential mononucleotides (foe). Here, the occurrence, synthesis, degradation, and proposed functions of these compounds are briefly reviewed, along with some new data and recent evidence supporting roles for Ap3A and Ap4A in the cellular decision making processes leading to proliferation, quiescence, differentiation, and apoptosis. Hypotheses are forwarded for the involvement of Ap4A in the intra-S phase DNA damage checkpoint and for Ap3A and the pFhit (fragile histidine triad gene product) protein in tumour suppression. It is concluded that the roles of friend and foe are not incompatible, but are distinguished by the concentration range of nucleotide achieved under different circumstances.
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