KEAP1 Antibodies

Structure of KEAP1

KEAP1 is a cellular regulatory protein with a molecular weight of approximately 69 kDa. Its precise weight fluctuates within the range of 67-71 kDa due to species differences and transcript splicing variations.

The KEAP1 protein contains 627 amino acids and adopts a unique five-domain architecture (BTB-IVR-DGR-CTR-NTR). Its tertiary structure presents a typical β -folded barrel topology, with six Kelch repeat units jointly forming the NRF2 binding groove. It is particularly worth noting the conserved cysteine residues (Cys151, Cys273, Cys288) in the IVR domain. These residues act as electrophilic stress sensors and undergo covalent modification and conformational changes during oxidative stress, thereby releasing the regulation of NRF2 degradation.

Fig. 1 Domain organization of human Keap1.¹

Key structural properties of KEAP1:

• Unique BTB-Kelch dual-domain architecture
• The β-folded barrel 3D topology constitutes the NrF2-binding cavity
• Conserved cysteines in the IVR junction region serve as REDOX sensors

Functions of KEAP1

The core function of the KEAP1 protein is to act as a molecular switch for cellular oxidative stress responses. In addition, it is also involved in important physiological processes such as proteasome degradation, autophagy regulation and cell cycle management.

The KEAP1-NRF2 interaction presents a typical "hinge-latch" dual-site binding mode (ETGE-DLG configuration), where the high affinity binding of the ETGE motif provides a molecular basis for stress response, while the easy dissociation property of the DLG motif constitutes the structural prerequisite for degradation regulation.

Applications of KEAP1 and KEAP1 Antibody in Literature

1. Yu, Chao, and Jian-Hui Xiao. "The Keap1‐Nrf2 system: a mediator between oxidative stress and aging." Oxidative medicine and cellular longevity 2021.1 (2021): 6635460. https://doi.org/10.1155/2021/6635460

The article indicates that the Keap1-Nrf2 system is a key pathway for regulating oxidative stress and is closely related to aging. This pathway regulates antioxidant responses through KEAP1-cysteine modification, Nrf2 phosphorylation, and PI3K/Akt signaling, and its interaction with the mTOR pathway also provides a new direction for the development of anti-aging drugs.

2. Li, Jiucui, et al. "Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway." Journal of Translational Medicine 19.1 (2021): 96. https://doi.org/10.1186/s12967-021-02745-1

The article indicates that the Keap1-Nrf2 system is the core pathway for cells to respond to oxidative stress and is closely related to the aging process. This pathway regulates antioxidant responses through KEAP1-cysteine modification, Nrf2 phosphorylation, and cross-dialogue with signaling networks such as PI3K/Akt and mTOR, providing a key theoretical basis for the development of anti-aging drugs.

3. Tossetta, Giovanni, et al. "Modulation of NRF2/KEAP1 signaling in preeclampsia." Cells 12.11 (2023): 1545. https://doi.org/10.3390/cells12111545

This study focuses on the role of the KEAP1-NRF2 signaling pathway in the pathogenesis of preeclampsia. This pathway resists placental oxidative stress by regulating the expression of antioxidant genes. The article delves deeply into the cellular regulatory factors of this pathway and reviews the natural and synthetic compounds that can regulate this pathway, providing potential targets for the treatment of preeclampsia.

4. Zhou, Yunjiang, et al. "FAM117B promotes gastric cancer growth and drug resistance by targeting the KEAP1/NRF2 signaling pathway." The Journal of Clinical Investigation 133.3 (2023). https://doi.org/10.1172/JCI158705

This study reveals that FAM117B inhibits the ubiquitination and degradation of NRF2 by competitively binding to KEAP1 with NRF2, thereby activating the KEAP1/NRF2 signaling pathway. This mechanism promotes the proliferation of gastric cancer cells and chemotherapy resistance. Moreover, the co-high expression of FAM117B and NRF2 in cancer tissues suggests a poor prognosis for patients, indicating that it can serve as a potential therapeutic target.

5. Dewanjee, Saikat, et al. "Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management." Cell Communication and Signaling 22.1 (2024): 497. https://doi.org/10.1186/s12964-024-01878-2

This study focuses on the dual role of the Keap1-Nrf2/ARE pathway in brain cancer. This pathway can not only inhibit tumors, but its excessive activation can also promote the survival of cancer cells. The article focuses on the plant secondary metabolites that regulate this pathway in a KeAP1-dependent manner, providing potential strategies for the treatment of brain tumors.

Creative Biolabs: KEAP1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality KEAP1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom KEAP1 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our KEAP1 antibodies, custom preparations, or technical support, contact us at email.