Cellular regulation by soluble inositol phosphate messengers has yielded surprising knowledge that reaches well beyond the rigorously characterized regulation of Ca2+ release by inositol 1,4,5-trisphosphate (IP3), the best-known inositol phosphate. Inositol pyrophosphates belong to the diverse family of inositol polyphosphate species that have a range of signaling functions. The best-characterized inositol pyrophosphates are diphosphoinositol pentakisphosphate (IP7) and the bis-diphosphoinositol tetrakisphosphate (IP8). The activity of inositol pyrophosphates appears to be related to their rapid turnover in cells and also to their pyrophosphate groups, considered to contain high-energy bonds and unique signaling molecules implicated in regulation of processes, including apoptosis, telomere maintenance or vesicular trafficking. Inositol phosphate signaling molecules can directly mediate protein phosphorylation, a new way in which signals can be transduced in cells. Another phosphate molecule, inorganic polyphosphate (poly P), found in every living-cell, is a chain of many tens or hundreds of phosphate residues linked by the same phosphoanhydride bonds as in ATP. Poly P likely was a phosphorylating agent and catalyst of peptide bond formation in prebiotic times. It has been shown that poly P is essential in stringent response, survival for bacterial responses to stresses, starvation and pathogenesis. Yeast mutants, affected in enzymes of the inositol pyrophosphate synthesis have reduced intracellular poly P levels suggesting that inositol pyrophosphates are necessary for poly P synthesis and maintenance. The mechanism by which inositol pyrophosphates are able to transduce the cellular phosphate status into a cascade of signaling events is unknown. The present proposal tries to find links between inositol polyphosphate and poly P in relation to poly P synthesis and their role in cell signaling.
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