http://www.cnr.it/ontology/cnr/individuo/prodotto/ID5083
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
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
- 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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