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J. Biol. Chem. 275 (39): 30520-30524
© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
A Role for Nuclear Phospholipase C 1 in Cell Cycle
Control*
Irene
Faenza ,
Alessandro
Matteucci§,
Lucia
Manzoli ,
Anna
Maria
Billi ,
Michela
Aluigi ,
Daniela
Peruzzi ,
Marco
Vitale¶,
Sergio
Castorina ,
Pann-Ghill
Suh**, and
Lucio
Cocco 
From the Department of Anatomical Sciences, Cellular
Signalling Laboratory, University of Bologna, Via Irnerio 48, I-40126 Bologna, Italy the § Institute of Cytomorphology,
CNR c/o Rizzoli Institute, I-40136 Bologna, Italy, the
¶ Department of Biomedical Sciences and Biotechnology, University
of Brescia, I-25123 Brescia, Italy, the Department of Anatomy,
University of Catania, I-95124 Catania, Italy, and the ** Department of
Life Sciences, Division of Molecular Life Science, Pohang University of
Science and Technology, 633-165 Pohang, South Korea
Phosphoinositide signaling resides in the
nucleus, and among the enzymes of the cycle, phospholipase C (PLC)
appears as the key element both in Saccharomyces cerevisiae
and in mammalian cells. The yeast PLC pathway produces multiple
inositol polyphosphates that modulate distinct nuclear processes. The
mammalian PLC 1, which localizes in the nucleus, is
activated in insulin-like growth factor 1-mediated mitogenesis and
undergoes down-regulation during murine erythroleukemia
differentiation. PLC 1 exists as two polypeptides of 150 and 140 kDa generated from a single gene by alternative RNA splicing,
both of them containing in the COOH-terminal tail a cluster of lysine
residues responsible for nuclear localization. These clues prompted us
to try to establish the critical nuclear target(s) of
PLC 1 subtypes in the control of cell cycle progression. The results reveal that the two subtypes of PLC 1 that
localize in the nucleus induce cell cycle progression in Friend
erythroleukemia cells. In fact when they are overexpressed in the
nucleus, cyclin D3, along with its kinase (cdk4) but not cyclin
E is overexpressed even though cells are serum-starved. As a
consequence of this enforced expression, retinoblastoma protein is
phosphorylated and E2F-1 transcription factor is activated as well. On
the whole the results reveal a direct effect of nuclear
PLC 1 signaling in G1 progression by means of
a specific target, i.e. cyclin D3/cdk4.
*
This work was supported by the Italian Association for
Cancer Research, Italian Murst Cofin99, Selected Topics Research Fund of Bologna University, and Italian CNR PF Biotechnology grants.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.

To whom correspondence should be addressed. E-mail:
lcocco@biocfarm.unibo.it.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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