In support of this hypothesis, others have shown hypoxia-induced proteolysis of the α-secretases ADAM10 and TACE without alteration in mRNA levels in neuroblastoma [45], and of the MYC oncogene in human colon carcinoma cells and primary human keratinocytes, involving the ubiquitin ligases FBXW7 and DDB1, and cathepsins D and S [46]. The gene discussed is CTSD; the disease is colon carcinoma.