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Phosphoinositide Signaling in Nuclei of Friend Cells: Tiazofurin Down-Regulates Phospholipase C ß₁¹

Institute of Human Morphology, University of Chieti, Via dei Vestini, 66013 Chieti [L. M.]; Institute of Anatomy, University of Bologna, Via Irnerio, 48, 40126 Bologna [A. M. B., L. C.]; Department of Morphology, University of Trieste, Via Manzoni, 16, 34138 Trieste [A. M. M.]; Institute of Cytomorphology, Consiglio Nazionale delle Ricerche and Laboratory for Electron Microscopy and Cell Biology, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy [A. M., S. R.]; Department of Molecular and Cellular Physiology, AFRC, Babraham Institute, Babraham, Cambridge CB2 4AT, England [R. S. G.]; and Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5200 [G. W.]

Previous investigations have demonstrated the presence of conventional lipid kinases and phospholipase C (PLC) activities in nuclei of Friend erythroleukemia cells. Moreover, when Friend erythroleukemia cells are treated for 96 h with the antitumor drug tiazofurin, the induction of erythroid differentiation is accompanied by changes in amounts of both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate due to the inhibition of an uncharacterized nuclear PLC activity. Here, we show that the nuclear PLC ß₁ isoform is down-regulated by tiazofurin (5 µM) treatment of Friend erythroleukemia cells as shown by both Western blot and Northern blot analyses for PLC ß₁ message. This indicates that PLC ß₁ down-regulation is tightly linked with erythroid differentiation of Friend erythroleukemia cells and that the autonomous nuclear signaling via inositol lipid cycle can be controlled by the antitumor drug tiazofurin.

¹ This work was supported by Italian Consiglio Nazionale delle Ricerche Grants PF IG and PF ACRO and by AFRC International Scientific Interchange Scheme.

² To whom requests for reprints should be addressed.

Received 4/17/95. Accepted 6/ 2/95.

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