Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical and structural mechanisms without new human data.
PubMed 27497696 · doi:10.1016/j.abb.2016.08.005
What was done
This narrative review summarizes structural and biochemical findings on Kelch-like ECH associated protein 1 (Keap1). It describes Keap1's role in a Cullin3-based Cullin-RING E3 ubiquitin ligase complex, its interaction with transcription factor Nrf2, and how its reactive cysteine residues detect electrophiles and oxidants.
What was found
The abstract reports purely qualitative molecular mechanisms with no numerical data. Keap1 acts as a homodimeric substrate adaptor targeting Nrf2 for ubiquitination and degradation. Electrophilic and oxidative inducers chemically modify reactive cysteine sulfhydryl groups on Keap1, impairing Nrf2 degradation and enabling Nrf2 to accumulate, enter the nucleus, and drive cytoprotective gene transcription.
Why it matters
It outlines the fundamental biochemical mechanism by which mammalian cells detect oxidative and electrophilic stress to mount an adaptive cytoprotective response.
Limits
The abstract describes a narrative review of molecular and structural studies with no quantitative metrics, meta-analytic methods, or direct human clinical data.
Cited by
- supports Isothiocyanates bind to reactive cysteine sulfhydryl groups on Keap1, inducing a conformational change in the protein.