DOMAINS AND SIGNALLING PATHWAYS IN THE NUCLEUS

L. Cocco | Department of Biomedical & Neuromotor Sciences, University of Bologna Medical School, Bologna. Italy

Since 1987 evidence from several laboratories has highlighted the presence of autonomous nuclear inositol lipid metabolism¹. The evidence suggests that lipid signalling molecules are important components of signalling pathways operating within the nucleus. The findings are important given the fact that nuclear signalling activity controls cell growth and differentiation. Among the nuclear enzymes involved in this system, inositide-specific phospholipase C (PI-PLC) β1 has been one of the most extensively studied enzymes². Besides the studies on its signalling activity in physiological conditions, clinically oriented ones have shown that PI-PLCβ1 gene is associated with several pathological conditions. Nuclear PI-PLCβ1 is involved in the early stages of hemopoiesis and, namely, in the control of cell-cycle progression in progenitor hemopoietic cells. In addition, nuclear PI-PLCβ1 plays a crucial role in the initiation of the genetic program responsible for muscle differentiation in that the enzyme activates the cyclin D3 promoter during the differentiation of myoblasts to myotubes. Down regulation of this enzyme is associated with progression of myelodysplastic syndromes (MDS) into acute myeloid leukaemia as well as with myotonic dystrophy or DM, both type 1 and type 2. Here we briefly highlight the most important evidence of the role of nuclear PI-PLCβ1 in these pathologies as well as the significance of subcellular localization of PI-PLCs. In addition, it is quite clear the potential role of PLCβ1 as biomarker in high-grade gliomas.