What question did this study set out to answer?

To determine how Keap1 mediates the rapid proteasomal turnover and degradation of the antioxidant transcription factor Nrf2 under basal conditions.

July 28, 2004Molecular and Cellular BiologyOpen Access

Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2

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To determine how Keap1 mediates the rapid proteasomal turnover and degradation of the antioxidant transcription factor Nrf2 under basal conditions.
Evaluated the turnover rate and degradation requirements of Nrf2 using protein binding assays.
Performed domain function mapping of Keap1, focusing on its BTB and intervening-region (IVR) domains.
Analyzed in vivo protein-protein interactions between Keap1 and the Cul3-Roc1 E3 ubiquitin ligase complex.
Direct association between Keap1 and Nrf2 is required for rapid Nrf2 degradation, maintaining its half-life at less than 20 minutes under basal conditions.
Keap1 binds the N-terminal region of Cul3 via its IVR domain and requires both BTB and IVR domains to promote Cul3-Roc1-mediated ubiquitination and degradation of Nrf2.

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Implication

Mechanistic study demonstrates that Keap1 acts as a Cul3-based E3 ligase adaptor mediating Nrf2 degradation in mammalian cells, revealing key pathways controlling cellular stress responses.

Cite This Study

Kobayashi et al. (2004) studied this question.

synapsesocial.com/papers/6a088074ab15ea61dee8e42c https://doi.org/10.1128/mcb.24.16.7130-7139.2004

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Implication

Mechanistic study demonstrates that Keap1 acts as a Cul3-based E3 ligase adaptor mediating Nrf2 degradation in mammalian cells, revealing key pathways controlling cellular stress responses.

Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2

Key Points

Discussion

Implication

Cite This Study

Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2

Key Points

Discussion

Implication

Cite This Study

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