Phosphoinositides II: The Diverse Biological Functions

Fiume R, Keune WJ, Faenza I, Bultsma Y, Ramazzotti G, Jones DR, Martelli AM, Somner L, Follo MY, Divecha N, Cocco L, Fiume, Roberta, Keune, Willem Jan, Faenza, Irene, Bultsma, Yvette, Ramazzotti, Giulia, Jones, David R., Martelli, Alberto M., Somner, Lilly, Follo, Matilde Y., Divecha, Nullin, Cocco, Lucio, Roberta Fiume, Willem Jan Keune, Irene Faenza, Yvette Bultsma, Giulia Ramazzotti, David R. Jones, Alberto M. Martelli, Lilly Somner, Matilde Y. Follo, Nullin Divecha, Lucio Cocco

Lipid signalling in human disease is an important field of investigation and stems from the fact that phosphoinositide signalling has been implicated in the control of nearly all the important cellular pathways including metabolism, cell cycle control, membrane trafficking, apoptosis and neuronal conduction. A distinct nuclear inositide signalling metabolism has been identified, thus defining a new role for inositides in the nucleus, which are now considered essential co-factors for several nuclear processes, including DNA repair, transcription regulation, and RNA dynamics. Deregulation of phoshoinositide metabolism within the nuclear compartment may contribute to disease progression in several disorders, such as chronic inflammation, cancer, metabolic, and degenerative syndromes. In order to utilize these very druggable pathways for human benefit there is a need to identify how nuclear inositides are regulated specifically within this compartment and what downstream nuclear effectors process and integrate inositide signalling cascades in order to specifically control nuclear function. Here we describe some of the facets of nuclear inositide metabolism with a focus on their relationship to cell cycle control and differentiation.