Abstract
Nrf2 is the key transcription factor regulating the antioxidant response. Nrf2 signaling is repressed by Keap1 at basal condition and induced by oxidative stress. Keap1 is recently identified as a Cullin 3-dependent substrate adaptor protein. A two-sites binding ''hinge & latch'' model vividly depicts how Keap1 can efficiently present Nrf2 as substrate for ubiquitination. Oxidative perturbation can impede Keap1-mediated Nrf2 ubiquitination but fail to disrupt Nrf2/Keap1 binding. Nrf2 per se is a redox-sensitive transcription factor. A new Nrf2-mediated redox signaling model is proposed based on these new discoveries. Free floating Nrf2 protein functions as a redox-sensitive probe. Keap1 instead functions as a gate keeper to control the availability of Nrf2 probes and thus regulates the overall sensitivity of the redox signaling.
Original language | English (US) |
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Pages (from-to) | 91-104 |
Number of pages | 14 |
Journal | Molecular Carcinogenesis |
Volume | 48 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2009 |
Externally published | Yes |
Keywords
- Keap1
- Nrf2
- Redox
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research