Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane: implications of posttranslational modifications.
Level 5 - mechanism / opinion, no new human data
Narrative review of molecular mechanisms and posttranslational modifications
PubMed 21793854 · doi:10.1111/j.1749-6632.2011.06092.x
What was done
This paper reviews the molecular mechanisms by which the dietary isothiocyanate sulforaphane regulates transcription factor Nrf2 through the Cullin3/Keap1 E3 ubiquitin ligase pathway, focusing on posttranslational modifications of Keap1 and Nrf2.
What was found
The abstract reports no empirical or quantitative data. It summarizes qualitatively that sulforaphane reacts as an electrophile with protein thiols on Keap1 cysteine residues to form thionoacyl adducts, inhibiting Nrf2 polyubiquitination and degradation. It also describes potential modulation of intracellular kinases that phosphorylate Nrf2 to control its stability and nucleocytoplasmic trafficking, driving antioxidant response element (ARE)-dependent gene activation.
Why it matters
It outlines the biochemical framework for sulforaphane-mediated chemoprevention, identifying specific electrophilic adduct formation on Keap1 and kinase-mediated phosphorylation as central regulatory nodes.
Limits
The abstract contains no primary quantitative measurements, sample sizes, or systematic review methodology. The described mechanisms reflect bench and theoretical models without in vivo human clinical or pharmacokinetic data reported.
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