SKP2 and hepatocellular carcinoma: For instance, Huang et al. indicated that HBx with mutations in the core promoter region deregulated S phase kinase-associated protein 2 (SKP2), a member of the F-box family that acts as a substrate-specific adaptor in the SCF E3 ligase complex, to decrease the stability of its target protein p21 [87], and induce the changes in the cell cycle to facilitate the proliferation of HCC cells.