Mel-18 and Bmi-1 are mammalian homologs of Drosophila Pc-g group proteins, as they are similarly expressed during development and implicated in the regulation of gene expression, axial skeleton development, and the control of proliferation and survival of hematopoietic cells. Mel-18 directly binds to DNA through a ring-finger motif and preferentially associates with juxtaposed enhancer elements on various genes, including Bcl-2, c-Myc and Hox. Mel-18 is an immediate early response gene within the c-Myc/Cdc25 signaling cascade that exhibits tumor suppressor activity and negatively regulates cell cycle progression by blocking S phase entry. Alternatively, Bmi-1 has been identified as a potent oncogene as it contributes to the transcriptional activation of genes implicated in early lymphoid development.