title: Nuclear phosphoinositides and their roles in cell biology and disease.
abstract: Since the late 1980s, a growing body of evidence has documented that phosphoinositides and their metabolizing enzymes, which regulate a large variety of cellular functions both in the cytoplasm and at the plasma membrane, are present also within the nucleus, where they are involved in processes such as cell proliferation, differentiation, and survival. Remarkably, nuclear phosphoinositide metabolism operates independently from that present elsewhere in the cell. Although nuclear phosphoinositides generate second messengers such as diacylglycerol and inositol 1,4,5 trisphosphate, it is becoming increasingly clear that they may act by themselves to influence chromatin structure, gene expression, DNA repair, and mRNA export. The understanding of the biological roles played by phosphoinositides is supported by the recent acquisitions demonstrating the presence in the nuclear compartment of several proteins harboring phosphoinositide-binding domains. Some of these proteins have functional roles in RNA splicing/processing and chromatin assembly. Moreover, recent evidence shows that nuclear phospholipase Cβ1 (a key phosphoinositide metabolizing enzyme) could somehow be involved in the myelodysplastic syndrome, i.e. a hematopoietic disorder that frequently evolves into an acute leukemia. This review aims to highlight the most significant and updated findings about phosphoinositide metabolism in the nucleus under both physiological and pathological conditions.
authors.affiliation: Department of Human Anatomy, University of Bologna, Bologna, Italy. alberto.martelli@unibo.it
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Ognibene
authors.forename: Francesca
authors.initials: F
authors.lastname: Buontempo
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
authors.forename: Daniela
authors.initials: D
authors.lastname: Bressanin
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Camilla
authors.initials: C
authors.lastname: Evangelisti
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism; D010770:Phosphotransferases / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000737:chemistry / Q000378:metabolism
chemical_list: D010716:Phosphatidylinositols; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D010738:Type C Phospholipases