Nuclear inositide signaling: an appraisal of phospholipase C beta 1 behavior in myelodysplastic and leukemia cells. (Articolo in rivista)

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Label
  • Nuclear inositide signaling: an appraisal of phospholipase C beta 1 behavior in myelodysplastic and leukemia cells. (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cocco L, Follo MY, Faenza I, Bavelloni A, Billi AM, Martelli AM, Manzoli L. (2007)
    Nuclear inositide signaling: an appraisal of phospholipase C beta 1 behavior in myelodysplastic and leukemia cells.
    in Advances in enzyme regulation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cocco L, Follo MY, Faenza I, Bavelloni A, Billi AM, Martelli AM, Manzoli L. (literal)
Pagina inizio
  • 2 (literal)
Pagina fine
  • 9 (literal)
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  • 47 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Cellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy; Laboratory of Cell Biology and Electron Microscopy, IOR, Bologna, Italy; ITOI-CNR, Bologna Unit, c/o IOR, Bologna, Italy; School of Pharmacy, University of Bologna, Italy. (literal)
Titolo
  • Nuclear inositide signaling: an appraisal of phospholipase C beta 1 behavior in myelodysplastic and leukemia cells. (literal)
Abstract
  • Phospholipids are key regulators of a large number of cellular functions and do not act merely as structural components of biological membranes. Among phospholipids, polyphosphoinositides are key players in a number of signaling pathways. Inositol phospholipids are quantitatively minor constituents of cell membranes. Indeed, phosphatidylinositol (PI) typically comprises approximately 10% of total membrane lipid. This hints at the fact that inositol lipids are likely to play a major functional role. The pioneering work of Hokin and Hokin (1953) published more than 50 years ago, showed that stimulation of pancreas and brain slices with cholinergic agonists was accompanied by enhanced incorporation of [32P]orthophosphate selectively into PI, but not into other phospholipids. We are now aware that this effect re.ects a compensatory resynthesis of phosphoinositides which follows the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by receptor-regulated forms of phosphoinositide-speci.c phospholipase C (PI-PLC). This reaction generates two products, inositol 1,4,5-trisphosphate (IP3), and diacylglycerol (DAG), which are both key second messengers in the control of many cell functions (Divecha and Irvine, 1995; Payrastre et al., 2001). The discovery of the second messenger role of IP3 and DAG has brought phosphoinositide signaling to the very forefront of biological and biomedical research. Signaling through various phosphoinositides, including 3-phosphorylated inositol lipids, has been shown to mediate cell growth and differentiation, apoptosis, intracellular vesicle traf.cking, ion channel activation, insulin action, cytoskeletal changes, and motility (Toker, 2002). In addition, it is now clear that phosphoinositide signaling disorders are implicated in the pathogenesis of a number of human diseases ranging from cancer to type 2 diabetes (Pendaries et al., 2003). Phosphoinositide signaling involves the generation of lipid second messengers in response to stimuli in a receptor-mediated manner at the plasma membrane. However, the existence of a nuclear PI metabolism independent from that occurring elsewhere in the cells now part of the story (Martelli et al., 1999), suggesting that the nucleus constitutes both a functional and a distinct compartment for PI metabolism (Martelli et al., 2003). Indeed, it has been demonstrated that nuclei contain many of the enzymes involved in the classical PI cycle, including kinases required for the synthesis of PIP2, PI-PLC, and diacylglycerol kinase (Bregoli et al., 2001; Cocco et al., 2001; D’Santos et al., 1998; Irvine, 2003; Martelli et al., 1999, 2002a; Tu-Sekine and Raben, 2004). It is extremely important that speci.c changes in the nuclear PI metabolism have been implicated in cell growth, differentiation, and neoplastic transformation (Divecha et al., 2000; Martelli et al., 2002b; Tamiya-Koizumi, 2002). In addition, the nucleus also contains 3-phosphorylated inositol lipids and the enzymes which synthesize them, i.e. phosphoinositide 3-kinases (Neri et al., 2002). The 3-phosphorylated lipids are not substrates for any known PI-PLC but act themselves as second messengers (Vanhaesebroeck et al., 2001). Among the enzymes of the inositol lipid cycle, it is well known that PI-PLCb1 is a key enzyme in nuclear signal transduction, and it is involved in many cellular processes such as proliferation and differentiation (Cocco et al., 2005). In particular, the involvement of the PI-PLCb1 in the hemopoietic differentiation prompted us and others to investigate this signaling molecule in hematological malignancies. Indeed by using .uorescence in situ hybridization (FISH) analysis it has been previously evidenced that in blasts from high-risk myelodysplastic syndrome (MDS) patients, with normal GTG banding, and a fatal outcome, the PI-PLCb1 gene undergoes a monoallelic and interstitial deletion (Lo Vasco et al., 2004). Moreover in Friend erythroleukemia cells, Felc, nuclear PI PLCb1 targets speci.cally the promoter region of genes involved in cell growth and differentiation as well (Cocco et al., 2006b; Fiume et al., 2005). Here we are keen to review some new data which hint at the fact that the imbalance of the nuclear versus cytoplasmatic PI-PLCb1 signaling could affect the cell cycle progression of hematopoietic cells. (literal)
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