Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology (Articolo in rivista)

Type
Label
  • Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cocco L, Faenza I, Follo MY, Billi AM, Ramazzotti G, Papa V, Martelli AM, Manzoli L. (2009)
    Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology
    in Advances in enzyme regulation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cocco L, Faenza I, Follo MY, Billi AM, Ramazzotti G, Papa V, Martelli AM, Manzoli L. (literal)
Pagina inizio
  • 2 (literal)
Pagina fine
  • 10 (literal)
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  • 49 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
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  • Cellular Signaling Laboratory Department of Anatomical Sciences, University of Bologna, Bologna, Italy; IGM-CNR, Bologna Unit, c/o IOR, Bologna, Italy; School of Pharmacy, University of Bologna, Bologna, Italy (literal)
Titolo
  • Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology (literal)
Abstract
  • The existence of phospholipids in chromosomes has been suggested by the work of La Cour et al. (1958). In the 1970s, Manzoli and colleagues demonstrated that addition of phospholipids to purified nuclei could influence in vitro transcription (Manzoli et al., 1978). The same group demonstrated that negatively charged lipids led to chromatin decondensation, while positive charged lipids had the opposite effect. In 1987, the first demonstration came from a work by Cocco et al., that a nuclear PI metabolism exists and it is regulated during Friend cells differentiation (Cocco et al., 1987). Since then, progress has been made on the regulation of nuclear phosphoinositides (PI), as well as their role in cellular functions, i.e. growth and differentiation. Nevertheless, much still needs to be understood about the function, regulation and physical properties of this nuclear component. For example, while it is clear that these PIs are not part of the nuclear envelope but they reside within the nuclear domains, the physicochemical form of nuclear lipids still needs to be clarified (Irvine, 2006). We know that inositol lipid signaling molecules are essential components of the extremely complicated, multistep process that allows one extracellular signal to be transduced inside the cell, to the nucleus. In the nuclear compartment, lipid second messengers elicit reactions that regulate gene transcription, DNA replication or repair, and DNA cleavage, eventually resulting in cellular differentiation, proliferation, apoptosis and other cell functions. Inositol-containing phospholipids are the most intensively studied lipid second messengers. Albeit most of the research on signal transduction pathways based on PI has been devoted to phenomena that take place at the cell periphery and plasma membrane, it has become clear that the nuclear PI cycle is regulated in a totally independent manner from that at the plasma membrane level. This suggests that nuclear inositol lipids themselves can modulate nuclear processes, as important as transcription and pre-mRNA splicing, growth, proliferation, cell cycle regulation and differentiation. Phosphatidylinositol(4,5)bisphosphate (PIP2) is a key lipid molecule in the PI cycle. It is the substrate of enzymes involved in signal transduction, such as phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphoinositide 30-OH kinase (PI3K), thus producing the second messengers diacylglycerol (DAG), inositol trisphosphate (IP3) and phosphatidylinositol(3,4,5)trisphosphate (PIP3). PIP2 has also been shown to be directly involved in chromatin remodeling, by binding to proteins such as histone H1 and the Brahma-related gene associated factor (BAF) complex (Yu et al., 1998; Zhao et al., 1998). This double function of PIP2 in the nucleus, both as substrate for second messenger generation and as chromatin remodeling element, adds further emphasis to the importance of the enzymes responsible for nuclear PIP2 metabolism. In this review we shall focus on the nuclear PI-PLC, and only briefly consider nuclear PI3K and PIP kinases. In particular, we shall review the most update literature on PI-PLC b1, but it should be kept in mind that also PI-PLC g1 and PI-PLC d1 isoforms are present in the nucleus and function in a cell cycledependent manner. In particular, PI-PLC g1 is activated in the cytosol by receptor tyrosine kinases and translocates to the nucleus, where it acts as a guanine nucleotide exchange factor (GEF) for the nuclear GTPase PI3K enhancer (PIKE), which subsequently activates PI3K. (literal)
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