Interestingly, we found that USP22 strongly bound to the PPARγ DBD domain (Fig. 4g) as well as pVHL and CUL4B proteins in the HCC cells (Supplementary Fig. 6e), and the interaction between PPARγ and USP22 significantly decreased the pVHL and CRL4BAhR involved ubiquitination (Fig. 5d, e), indicating that USP22 regulates deubiquitination of PPARγ through other lysine sites. This evidence concerns the gene CUL4B and hepatocellular carcinoma.