FBXW2 reduction results in SKP2 accumulation to promote targeted ubiquitylation and degradation of a number of tumour suppressors and apoptosis-inducing substrates such as p21, p27, p130 and FOXO1, leading to the activation of the CDKs, E2F and mTOR pathway73 to promote cell proliferation and survival, eventually tumour formation. The gene discussed is SKP2; the disease is neoplasm.