wdr-23 Antibody
Description
WDR-23 in NRF2 Regulation
WDR-23 operates as an alternative to KEAP1 in controlling NRF2, a transcription factor critical for detoxification and oxidative stress responses.
Mechanistic Insights
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Proteasomal Degradation: WDR-23 recruits NRF2 to the CUL4-DDB1 complex, promoting its ubiquitination and degradation in the cytoplasm .
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Nuclear Regulation: WDR-23B isoform inhibits nuclear NRF2 by promoting protein turnover, reducing its ability to activate target genes .
Experimental Evidence
Impact on Cancer Therapy
WDR-23’s role in modulating NRF2 has implications for overcoming treatment resistance.
Chemotherapy Sensitivity
DNA Repair Modulation
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GEN1 Regulation: WDR-23 ubiquitinates GEN1 (a Holliday junction resolvase), affecting DNA repair efficiency. Nuclear WDR-23B promotes GEN1 turnover, while cytoplasmic WDR-23A stabilizes it .
Research Gaps and Future Directions
While WDR-23’s functions are well-documented, direct studies on WDR-23 antibodies are absent. Potential areas for investigation:
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Antibody Development: Tools for detecting WDR-23 isoforms or post-translational modifications could clarify its subcellular dynamics.
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Therapeutic Targeting: Antibodies blocking WDR-23 interactions with CUL4-DDB1 might enhance NRF2 activity in oxidative stress disorders.
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Research has identified and confirmed mutations in the xrep-2, xrep-3, and xrep-4 genes. xrep-2 corresponds to alh-6, an ortholog of the human gene associated with familial hyperprolinemia. The xrep-3 mutation is a gain-of-function allele of skn-1. xrep-4 encodes an F-box-containing protein and affects the stability of WDR-23 (xrep-1), a crucial regulator of SKN-1 (xrep-3). PMID: 28428286
- A missense mutation within the conserved F-box domain of XREP-4 significantly weakens its interaction with SKR-1, while maintaining its interaction with WDR-23. This leads to a substantial reduction in SKN-1-dependent gene activation. These findings support the notion that XREP-4 modulates the SKN-1 stress response by acting as a bridge between WDR-23 and the ubiquitin ligase component SKR-1. PMID: 28341649
- Studies have identified WDR23 as an alternative regulator of NRF2 protein stability. This discovery reveals a cellular pathway that independently controls NRF2 activity and its capacity for cytoprotection, distinct from the KEAP1 pathway. PMID: 28453520
- SKR-1/2 has been found to function upstream of the WD40 repeat protein WDR-23, which binds to and inhibits SKN-1. These findings highlight a novel p38 MAPK-independent signaling mechanism that activates SKN-1 through SKR-1/2 and involves WDR-23. PMID: 27776126
- Diverse phenotypic effects of wdr-23 are dependent on SKN-1. Beneficial and detrimental phenotypes of wdr-23 and skn-1 can be partially separated. Activation of SKN-1 delays degenerative tissue changes during aging. PMID: 26056713
- Research indicates that SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23. WDR-23 interacts with the CUL-4/DDB-1 ubiquitin ligase, likely targeting the transcription factor for proteasomal degradation. PMID: 19273594
