It has been suggested that deregulated MYCN expression in MYCN amplified neuroblastoma indirectly upregulates SKP2 via the induction of CDK4 (Figure 3), thereby reducing the abundance of repressive pRB-E2F1 complexes bound to the SKP2 promoter and providing an entry point into the SKP2 autoinduction loop (Muth et al., 2010). The gene discussed is SKP2; the disease is neuroblastoma.