Nuclear inositol lipid cycle: a new central intermediary in signal transduction.

The involvement of phospholipids and especially polyphosphoinositides in cellular signalling has been documented in detail over the last 20 years. Besides the membrane localisation the nucleus also has been show to be a site for both the synthesis and hydrolysis of the phosphorylated forms of phosphatidylinositol. Previous observations dealing with signal transduction have established phospholipase C, specific for inositol lipids (PLC), an important step in the inositol lipid cycle. Of the several known PLC isoforms the type beta 1 is of particular interest because of its reported nuclear localisation, in addition to its presence at the plasma membrane. Indeed, investigations from our laboratory and others have shown the existence in several cell types of an autonomous intranuclear inositide cycle endowed with both conventional lipid kinases and PLC. Moreover, both the stimulation and the inhibition of the nuclear PLC beta 1 under different stimuli implicate this PLC isoform as a key enzyme for mitogen-activated cell growth as well as for differentiation. These findings have prompted us to better characterise the nuclear PLC beta 1. The isoform beta 1 has been studied as a possible target for anti-cancer drugs and as an inducer, via diacylglycerol generation, of the translocation of specific protein kinase C (PKC) isozyme to the nucleus. The chromosome mapping of PLC beta 1 gene has been carried out and the effect of its knock-out by means of antisense cDNA has been determined.