Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology |
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| Authors: | Lucio Cocco Irene Faenza Matilde Y. Follo Anna Maria Billi Giulia Ramazzotti Veronica Papa Alberto M. Martelli Lucia Manzoli |
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| Affiliation: | aCellular Signaling Laboratory Department of Anatomical Sciences, University of Bologna, Bologna, Italy;bIGM-CNR, Bologna Unit, c/o IOR, Bologna, Italy;cSchool of Pharmacy, University of Bologna, Bologna, Italy |
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| Abstract: | The existence of an inositide-dependent nuclear signaling has been clearly shown. In this review we focused on the nuclear PI-PLC signaling activity and its downstream effects. The main isoform present in the nucleus is PI-PLC β1 and this isoform resides in the nuclear domains called speckles and colocalizes with the splicing factor SC35. PI-PLC β1 is also involved in the physiological control of the cell cycle. Moreover, acting on the cyclin D3 promoter plays a crucial role in the process of C2C12 myoblast differentiation. Finally in hematological malignancies such as high-risk MDS, the deletion of PI-PLC β1 gene has been observed. There is the likelihood that the deletion is a prognostic marker in that 66.7% MDS patients bearing the PI-PLC β1 monoallelic deletion evolved into AML. In addition the expression of nuclear PI-PLC β1 in MDS patients is modulated by the demethylating drug azacytidine. Therefore the analysis of nuclear PI-PLC-β1 appears useful for both MDS prognosis and checking of the epigenetic effect of antileukemic drugs. |
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