Journal of Biological Chemistry
Volume 275, Issue 39, 29 September 2000, Pages 30520-30524
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MECHANISMS OF SIGNAL TRANSDUCTION
A Role for Nuclear Phospholipase Cβ1 in Cell Cycle Control*

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Phosphoinositide signaling resides in the nucleus, and among the enzymes of the cycle, phospholipase C (PLC) appears as the key element both in Saccharomyces cerevisiaeand in mammalian cells. The yeast PLC pathway produces multiple inositol polyphosphates that modulate distinct nuclear processes. The mammalian PLCβ1, which localizes in the nucleus, is activated in insulin-like growth factor 1-mediated mitogenesis and undergoes down-regulation during murine erythroleukemia differentiation. PLCβ1 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 PLCβ1 subtypes in the control of cell cycle progression. The results reveal that the two subtypes of PLCβ1 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 PLCβ1 signaling in G1 progression by means of a specific target, i.e. cyclin D3/cdk4.

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Published, JBC Papers in Press, July 26, 2000, DOI 10.1074/jbc.M004630200

*

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.