Mel-18 overexpression is linked to c-myc downregulation, leading to BMI-1 decrease, p16 upregulation and ultimately to cell senescence.135 Interestingly, in flies, LOF of cPRC1 members results in upregulation of cancer-related genes, including genes involved in the Notch, JNK and JAK/STAT signaling pathways74,136,137 (Fig. 4b), a difference that might be due in part to the absence of PcG-mediated repression of the INK4a-ARF locus in flies. The gene discussed is CDKN2A; the disease is cancer.