NEDD8 and hepatocellular carcinoma: Finally, rescue experiments revealed that TAS4464 treatment (100 nM, 12 h), one of the most potent and selective small molecule NEDD8 activating enzyme inhibitors [31], significantly inhibited augmented PCNA NEDDylation, decreased PCNA polyubiquitination, and increased PCNA protein caused by NEDD8 overexpression in HCC cells (Fig. 5I and Supplementary Fig. 3G).