CUL3 and gallbladder cancer: It is well acknowledged that Nrf2 activation plays a critical role in various human cancers, such as hepatocellular carcinomas, lung cancer, and gallbladder cancer [31–33].Under basal conditions Nrf2 is polyubiquitinated by the Keap1-Cul3-E3 ligase and degraded by the 26S-proteasome.