USP22 and cancer: As shown in Fig. 6A, overexpression of AP2 drastically upregulated USP22 protein as well as Cyclin D1 (a downstream target of USP22) in both H1299 (left panel) and A549 (right panel) cancer cells, while overexpression of AP2 did not upregulate Cyclin D1 in USP22 knock-out (USP22−/−) H1299 and A549 cancer cells, (which was previously generated and reported [14]).