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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 Cbeta 1 in Cell Cycle Control*

Irene FaenzaDagger , Alessandro Matteucci§, Lucia ManzoliDagger , Anna Maria BilliDagger , Michela AluigiDagger , Daniela PeruzziDagger , Marco Vitale, Sergio Castorina||, Pann-Ghill Suh**, and Lucio CoccoDagger Dagger Dagger

From the Dagger  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 PLCbeta 1, which localizes in the nucleus, is activated in insulin-like growth factor 1-mediated mitogenesis and undergoes down-regulation during murine erythroleukemia differentiation. PLCbeta 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 PLCbeta 1 subtypes in the control of cell cycle progression. The results reveal that the two subtypes of PLCbeta 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 PLCbeta 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.

Dagger Dagger 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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