The Role of Sulfhydryl Reactivity of Small Molecules for the Activation of the KEAP1/NRF2 Pathway and the Heat Shock Response.

摘要: The KEAP1/NRF2 pathway and the heat shock response are two essential cytoprotective mechanisms that allow adaptation survival under conditions of oxidative, electrophilic, thermal stress by regulating expression elaborate networks genes with versatile protective functions. pathways independently regulated transcription factor nuclear factor-erythroid 2 p45-related (NRF2) 1 (HSF1), respectively. activity these transcriptional master regulators increases during also upon encounter small molecules (inducers), both naturally occurring as well synthetically produced. Inducers have a common chemical property: ability to react sulfhydryl groups. protein targets such sulfhydryl-reactive compounds equipped highly reactive cysteine residues, which serve sensors for inducers. initial cysteine-sensed signal is further relayed affect large genes, in turn can ultimately influence complex cell fate decisions life death. paper summarizes multiple lines experimental evidence demonstrating reactivity groups major determinant mechanism action molecule dual activators response.