KDM6B Antibodies

Structure of KDM6B

The molecular weight of the KDM6B protein is approximately 180 kDa and it varies among different species. This protein mainly catalyzes the demethylation of trimethylation of lysine at position 27 of histone H3 through the JmjC domain.

The full-length KDM6B contains approximately 1400 amino acids and has multiple functional domains. Its JmjC domain is located at the C-terminal end and relies on Fe²⁺and α-ketoglutarate to carry out demethylation reactions; the N-terminal TPR domain mediates protein interactions, while the ARID domain is involved in DNA binding. The entire protein removes the H3K27me3 modification, thereby relieving the inhibition on gene transcription. The TPR domain helps recruit to specific genomic regions, the ARID enhances substrate recognition specificity, and the active pocket at the center of the JmjC domain precisely accommodates the modified substrate and completes the catalysis.

Fig. 1 Mechanism of KDM6M in Gastric Cancer Development.¹

Key structural properties of KDM6B:

• The catalytic domain of JmjC is dependent on iron ions and α-ketoglutarate
• TPR domains mediate protein interactions with a variety of transcription factors
• ARID domains enhance substrate DNA binding specificity

Functions of KDM6B

The main function of KDM6B is to catalyze the demethylation of histone H3K27me3, thereby activating gene transcription. In addition, this protein is involved in various biological processes such as cell differentiation, inflammatory response, and tumor suppression.

The recognition of substrates by KDM6B is highly specific. Its JmjC domain strictly distinguishes between methylation and acetylation modifications, and also shows preferences for different methylation states (trimethylation vs. dimethylation). This substrate selectivity determines its unique position in the regulation of epigenetic transcription.

Applications of KDM6B and KDM6B Antibody in Literature

1. Liu, Fen, et al. "KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression." Cell Death & Disease 13.12 (2022): 1068. https://doi.org/10.1038/s41419-022-05458-5

The article indicates that KDM6B is upregulated in gastric cancer and is associated with poor prognosis. It can remove the H3K27me3 modification in the CXCR4 promoter region through its enzymatic activity, thereby upregulating CXCR4 expression and promoting the proliferation and metastasis of gastric cancer cells. Helicobacter pylori can induce the expression of KDM6B. Therefore, KDM6B is a potential oncogenic factor and therapeutic target for gastric cancer.

2. Jiang, Yuhang, et al. "KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma." Theranostics 11.8 (2021): 3868. https://doi.org/10.7150/thno.53347

The study reveals that the histone demethylase KDM6B is highly expressed in osteosarcoma and is associated with poor prognosis. KDM6B upregulates the expression of LDHA by removing the H3K27me3 modification in the promoter region of the LDHA gene, thereby promoting tumor metastasis. Targeted inhibition of KDM6B can significantly inhibit the migration and lung metastasis of osteosarcoma cells, suggesting its potential as a therapeutic target.

3. Xun, Jing, et al. "Cancer-derived exosomal miR-138-5p modulates polarization of tumor-associated macrophages through inhibition of KDM6B." Theranostics 11.14 (2021): 6847. https://doi.org/10.7150/thno.51864

The study found that breast cancer cells deliver miR-138-5p via exosomes to tumor-associated macrophages, inhibiting the expression of KDM6B in these cells. This process hinders the polarization of macrophages towards the M1 type and promotes the polarization towards the M2 type, thereby accelerating lung metastasis of the tumor. The level of circulating exosomal miR-138-5p is positively correlated with the progression of breast cancer, suggesting its potential as a prognostic marker and therapeutic target.

4. Gao, Yuen, Mohammad B. Aljazi, and Jin He. "Kdm6b haploinsufficiency causes ASD/ADHD-like behavioral deficits in mice." Frontiers in behavioral neuroscience 16 (2022): 905783. https://doi.org/10.3389/fnbeh.2022.905783

Studies have shown that insufficient dosage of KDM6B can lead to autism-like social impairments and attention deficit hyperactivity disorder-like behaviors in mice, such as excessive activity and impulsivity. This finding reveals the potential causal link between KDM6B gene mutations and neurodevelopmental disorders, providing an animal model for the study of related mechanisms.

5. Wu, Qiong, et al. "Evi1 governs Kdm6b-mediated histone demethylation to regulate the Laptm4b-driven mTOR pathway in hematopoietic progenitor cells." The Journal of Clinical Investigation 134.24 (2024). https://doi.org/10.1172/JCI173403

In this study, by inducing overexpression of EVI1 in mouse hematopoietic stem cells, a myelodysplastic syndrome model was established. It was revealed that this model upregulated KDM6B to remove the H3K27me3 modification of the target gene LAPTM4B, activating the mTOR pathway to promote malignant proliferation. This signaling axis was also present in patient samples, providing a new target for the treatment of related leukemia.

Creative Biolabs: KDM6B Antibodies for Research

Creative Biolabs specializes in the production of high-quality KDM6B antibodies for research and industrial applications. Our portfolio includes monoclonal and polyclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom KDM6B 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 KDM6B antibodies, custom preparations, or technical support, contact us at info@creative-biolabs.com.