Analysis of the new nuclear factor mel-18 which affects the development and signaltransduction of B cells

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mel-18 is a mammalian homologue of the Drosophila Polycomb group (PcG) gene encoding a sequence-specific transcriptional repressor. We found that the overexpression of mel-18 causes the cell cycle arrest of B-cells after stimulation of the BCR.Molecular analysis revealed that the downregulation of cyclin D2, cyclin E,CDK4, CDK6, CDK7, and CDC25A causes the impaired activities of cyclin-dependent kinases, resulting in hypophosphorylation of the Rb protein. We also demonstrated that c-myc is a direct target of Mel-18 and is downregulated upon mel-18 overexpression. c-Myc is known to regulate positively the expression of cdc25a and cyclin E.Thus we conclude that mel-18 negatively regulates the cell cycle progression through a new cascade starting from mel-18 to c-myc then cdc25a or cyclin E.