NFE2L2 and hepatocellular carcinoma: In addition, Komatsu and colleagues demonstrated that suppression of autophagy, which is accompanied by marked accumulation of p62, a selective autophagy substrate, contributes to the development of hepatocellular carcinoma through persistently activating nuclear factor (erythroid-derived 2)-like factor 2 (Nrf2), a transcriptional factor that activates gene expression of numerous cytoprotective genes [163,164].