Chapter 159 - Inositol Polyphosphate Regulation of Nuclear Function

Abstract

Over 30 inositol messengers are found in eukaryotic cells that may be generally grouped into two classes: inositol lipids or phosphoinositides (PIPs) and water-soluble inositol polyphosphates (IPs). Insights into the roles of these messengers have come through the characterization of numerous gene products that control the metabolism of PIPs and IPs, over eighty in humans and twenty-six in budding yeast. This chapter discusses in brief a small subset of the overall inositol signaling pathway, namely higher IPs, generally defined as having four or more phosphates. Two important concepts have emerged: one is the higher IPs discussed here are derived from phospholipase C-dependent activation, thus IP 3 is both a messenger and a precursor to others, and second is the higher IPs have been linked to the regulation of several nuclear processes. Emphasis will be placed on the gene products that synthesize IP 4 , IP 5 , IP 6 and diphosphoryl IPs and the processes they have been found to regulate. Several of these kinases appear to localize within the nucleus, and their activities are necessary for proper gene expression, mRNA export, and DNA metabolism. The breadth of nuclear processes regulated and the evolutionary conservation of the genes involved in their synthesis have sparked renewed interest in higher IPs as important intracellular messengers.