Fig. 1

USP7 inhibition upregulated USP22 in cancer cells. USP7 inhibitors FT671, P5091, and HBX41108 treatment upregulated USP22 in A. A549. B. H1299 and C. HCT116 cells in a dose-dependent manner. D. Knockdown of USP7 upregulated USP22 in A549 and H1299 lung cancer cells (Ctrl siRNA for control scramble siRNA). Protein was extracted from cells treated with USP7 inhibitors or siRNA for 72h for Western blot analysis. E. The upregulation of USP22 is dependent on the inhibition of USP7 deubiquitinase. Western blot analysis of USP22 of H1299 cells in which USP7 was first knocked down by siRNA transfection, 24h later, wild-type USP7 and a catalytically inactive USP7 mutant (C223S) plasmid were individually reintroduced to express the proteins to rescue upregulation of USP22 upon USP7 knockdown (Blk: without plasmid transfection, Ctrl: Control plasmid, Wt: wild type USP7, Mt: C223S loss-of-function USP7 mutant)