USP21 and hepatocellular carcinoma: In hepatocellular carcinoma cells, USP21 directly interacts with and stabilizes MEK2 by decreasing its K48-linked polyubiquitination, thus activating the MAPK/ERK branch, where MAPKKK is Raf, MAPKK is MEK, and MAPK is ERK (Figure 3) (Rushworth et al., 2006; Li et al., 2018).