Nuclear PLCbeta 1 affects CD24 expression in murine erythroleukemia cells

Fiume R, Faenza I, Matteucci A, Astolfi A, Vitale M, Martelli AM and Cocco L
Source: J Biol Chem
Publication Date: (2005)
Issue: 280(25): 24221-24226
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Species: mouse
Tissue Origin: blood
Nucleofector® I/II/2b
Inositide-specific phospholipase C (PLC) ss1 is a key enzyme in nuclear lipid signal transduction affecting cell cycle progression and may be directly involved in regulation of gene expression and hematopoiesis. By microarrays, we compared the effect of nuclear PLCss1 overexpression with that of PLC M2b cytoplasmatic mutant, which is exclusively located in the cytoplasm, in murine erythroleukemia cells. Out of 9000 genes analyzed, CD24 gene, coding for an antigen involved in differentiation as well as hematopoiesis as well, was up-regulated in cells overexpressing nuclear PLCss1 as compared to both cells overexpressing the M2b cytoplasmatic mutant and the wild type cells. Here we show that nuclear PLCss1 up-regulated the expression of CD24. The correlation was strengthened by the observation that when PLCss1 expression was silenced by means of siRNA CD24 expression was down-regulated. We also demonstrated that PLCss1-dependent up-modulation of CD24 was mediated, at least in part, at the transcriptional level, in that PLC1 affected the CD24 promoter activity. Moreover the up-regulation of CD24 was higher during erythroid differentiation of murine erythroleukemia cells. Altogether our findings, obtained by combining microarrays, phenotypic analysis and siRNA technology, identify CD24 as an molecular effector of nuclear PLCss1 signaling pathway in murine erythroleukemia cells and strengthen the contention that nuclear PLCss1 constitutes a key step in erythroid differentiation in vitro