KEAP1
KEAP1 is a substrate adaptor of the Cullin 3 (Cul3)-based E3 ubiquitin ligase complex that promotes ubiquitination and proteasomal degradation of the transcription factor Nrf2 under basal conditions[1][2].
Mechanistically, KEAP1 binds Nrf2 and recruits Cul3 through its BTB and intervening-region domains, thereby controlling Nrf2 stability and antioxidant response gene expression[1][2].
Oxidative and electrophilic stress modifies KEAP1 regulatory cysteine residues, resulting in Nrf2 stabilization and activation of Nrf2-dependent transcriptional responses[1].
In experimental models, disruption of KEAP1 or Cul3 increases Nrf2 nuclear accumulation and activates Nrf2 target genes, providing a framework for studying redox regulation and stress adaptation[2].
Compared with related isoforms, current evidence in these studies specifically defines KEAP1 as a Cul3 E3 ligase adaptor controlling Nrf2 degradation, while direct functional comparisons with other KEAP family isoforms are not established in the cited literature[1][2].
For research applications, KEAP1 modulation is investigated through genetic manipulation or chemical regulation of the KEAP1–Nrf2 pathway to examine oxidative stress responses and disease-associated cellular mechanisms[1][2].
Mechanistically, KEAP1 binds Nrf2 and recruits Cul3 through its BTB and intervening-region domains, thereby controlling Nrf2 stability and antioxidant response gene expression[1][2].
Oxidative and electrophilic stress modifies KEAP1 regulatory cysteine residues, resulting in Nrf2 stabilization and activation of Nrf2-dependent transcriptional responses[1].
In experimental models, disruption of KEAP1 or Cul3 increases Nrf2 nuclear accumulation and activates Nrf2 target genes, providing a framework for studying redox regulation and stress adaptation[2].
Compared with related isoforms, current evidence in these studies specifically defines KEAP1 as a Cul3 E3 ligase adaptor controlling Nrf2 degradation, while direct functional comparisons with other KEAP family isoforms are not established in the cited literature[1][2].
For research applications, KEAP1 modulation is investigated through genetic manipulation or chemical regulation of the KEAP1–Nrf2 pathway to examine oxidative stress responses and disease-associated cellular mechanisms[1][2].
References:
- [1]. Kobayashi A, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Molecular and Cellular Biology. 2004;24(16):7130-7139. [Content Brief]
- [2]. Cullinan SB, et al. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Molecular and Cellular Biology. 2004;24(19):8477-8486. [Content Brief]
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KEAP1 Related Products (1)
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