Inositides in the nucleus. Regulation of nuclear PI-plcbeta1 (Articolo in rivista)

Type
Label
  • Inositides in the nucleus. Regulation of nuclear PI-plcbeta1 (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cocco L., Martelli A.M., Vitale M., Falconi M., Bernabei O., Gilmour R.S., Manzoli F.A. (2002)
    Inositides in the nucleus. Regulation of nuclear PI-plcbeta1
    in Advances in enzyme regulation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cocco L., Martelli A.M., Vitale M., Falconi M., Bernabei O., Gilmour R.S., Manzoli F.A. (literal)
Pagina inizio
  • 181 (literal)
Pagina fine
  • 193 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 42 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • I.F. 2, 442 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Inositides in the nucleus. Regulation of nuclear PI-plcbeta1 (literal)
Abstract
  • It is now well established from the work of several independent laboratories that the presence of a nuclear inositol lipid metabolism is involved in the control of cell proliferation and differentiation.The evidence supporting the existence within thenucleus of a polyphosphoinositide cycle derives from the use of different methodologies, ranging from enzymaticactivity measurements in various nuclear subtractions to immunoelectron microscopy and, more recently, to molecular biology techniques. One of the most intriguing aspects of the nuclear polyphosphoinositide metabolism is that it is clearly distinct from the classic inositol lipid cycle located at plasma membrane level. Therefore, there are in the literature numerous examples of stimuli that selectively activate the nuclear cycle only. In the nuclear inositol lipid cycle a pivotal role is played by inositide-specific phospholipase C (PI- PLC)beta1, i.e.the enzyme that hydrolyzes phosphatidylinositol 4,5- bisphosphate (PtdIns(4,5) P2 ), yielding the two second messengers, diacylglycerol (DAG)and inositol 1,4,5-trisphosphate (Ins(1,4,5) P3 ). Nuclear PI-PLCbeta1 is activated in response to different stimuli such as insulin-like growth factor-I (IGF-I) and interleukin 1alpha. In IGF-I- treated Swiss 3T3 cells this activation resulted in increased intranuclear levels of DAG which are essential for attracting to this organelle the alpha isoform of protein kinase C (PKC). Very recent data coming from our laboratory highlighted the fact that nuclear PI-PLCbeta1 controls cell cycle progression conceivably through mechanisms involving cyclin D3 and its kinase cdk4. Despite the fact that intranuclear phosphoinositide metabolism was first described by us in 1987 (Cocco et al .1987),our knowledge about the mechanisms which control PI-PLCbeta1 was extremely limited. Although some investigations reported that GTP-bindin proteins could reside at the nuclear envelope, when we measured nuclear PI-PLC activity both in the presence and in the absence of GTP-gamma-S we did not find any difference in the enzymatic activity, suggesting that the mechanism of activation of nuclear PI-PLCbeta1 was independent from GTP- binding proteins. A good hint that a phosphorylative event was capable of stimulating nuclear PI-PLCbeta1 came from the evidence that when the cytoskeleton of Swiss 3T3 cells was depolymerized with colchicine, mitogen- activated protein kinase (MAPK) did not translocate to the nucleus and nuclear PI-PLCbeta1 was no longer activated upon mitogenic stimulation. Here we show that in three systems in which a mitogenic stimulus is given to quiescent cells, i.e.natural killer (NK) cells stimulated with interleukin-2 (IL-2), NIH 3T3 fibroblasts stimulated with insulin and Swiss 3T3 fibroblast stimulated with IGF-1, nuclear PI-PLCbeta1 undergoes phosphorylation in a serine residue, driven by activated MAPK which translocates to the nucleus. Moreover, we also have evidence that a negative feedback control mechanism involving PKCalpha attracted to thenucleus by DAG generated by nuclear PI-PLCbeta1 takes place and desensitizes nuclear inositol lipid cycle. (literal)

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