Ian M. Copple

TL;DR: The aim of this review is to summarise the current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking NRF2.

TL;DR: A physical and functional interaction between Keap1 and SQSTM1 is demonstrated and an additional layer of regulation in the Keap 1-Nrf2 pathway is revealed.

TL;DR: Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas, which may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions.

TL;DR: It is shown that brusatol provokes a rapid and transient depletion of Nrf2 protein, through a posttranscriptional mechanism, in mouse Hepa-1c1c7 hepatoma cells, substantiate brusatols as a useful experimental tool for the inhibition of NRF2 signaling and highlight the potential for therapeutic inhibition ofNrf2 to alter the risk of adverse events by reducing the capacity of nontarget cells to buffer against chemical and oxidative insults.

TL;DR: Historical and recent advances in understanding of the molecular mechanisms that regulate the activity of the Keap1-Nrf2 pathway are highlighted, alongside the emerging role of Nrf2 in promoting oncogenesis and chemotherapeutic drug resistance.