Kbtbd7, Kelch repeat and BTB domain containing 7, is a protein that functions as a transcriptional activator and a substrate adaptor in the ubiquitination process. It belongs to the BTB-kelch protein family and is involved in multiple signaling pathways, such as MAPK and NF-κB signaling [4,2]. Kbtbd7 has been shown to be important in various biological processes including brain development, and in pathological conditions like excessive inflammation after myocardial infarction [2]. Genetic models, especially gene knockout models, can be valuable in further elucidating its functions.

Knockdown of Kbtbd7 in in vitro models (human alveolar epithelial cells induced with lipopolysaccharide) reduced the inflammatory response, inhibited ROS production, ferroptosis, and mitochondrial dysfunction. In vivo, knocking down Kbtbd7 in septic lung injury mice improved lung tissue damage, inhibited inflammatory factors, ROS production, and ferroptosis, suggesting it could be a therapeutic target for septic lung injury [3]. In microglia, knockdown of Kbtbd7 inhibited LPS-induced pro-inflammatory cytokine release, as well as the activation of NLRP3 inflammasome and NF-κB signaling pathway, revealing its role in septic brain injury [5]. In non-small cell lung cancer (NSCLC), downregulation of Kbtbd7 inhibited cell proliferation and invasion. Kbtbd7 enhanced ubiquitin-dependent degradation of PTEN, activating EGFR/PI3K/AKT signaling and promoting NSCLC cell progression [1].

In conclusion, Kbtbd7 is involved in inflammation, cell proliferation, and invasion. Model-based research, especially knockdown and knockout studies, has revealed its role in diseases like septic lung injury, septic brain injury, and NSCLC. Understanding Kbtbd7's functions provides potential therapeutic strategies for these diseases.

References:

1. Zou, Zifang, Zhang, Bo, Li, Zhihan, Xu, Shun, Li, Qingchang. 2022. KBTBD7 promotes non-small cell lung carcinoma progression by enhancing ubiquitin-dependent degradation of PTEN. In Cancer medicine, 11, 4544-4554. doi:10.1002/cam4.4794. https://pubmed.ncbi.nlm.nih.gov/35499228/

2. Yuan, Chunju, Chen, Zhongpu, Zhou, Qianxing. 2022. Crocin inhibits KBTBD7 to prevent excessive inflammation and cardiac dysfunction following myocardial infarction. In Molecular medicine reports, 27, . doi:10.3892/mmr.2022.12907. https://pubmed.ncbi.nlm.nih.gov/36484363/

3. Li, Xiang, Lin, Zhao, Xu, ShiYu, Zhou, Jun, Liao, Bo. 2024. Knockdown of KBTBD7 attenuates septic lung injury by inhibiting ferroptosis and improving mitochondrial dysfunction. In International immunopharmacology, 133, 112129. doi:10.1016/j.intimp.2024.112129. https://pubmed.ncbi.nlm.nih.gov/38652964/

4. Hu, Junjian, Yuan, Wuzhou, Tang, Ming, Deng, Yun, Wu, Xiushan. . KBTBD7, a novel human BTB-kelch protein, activates transcriptional activities of SRE and AP-1. In BMB reports, 43, 17-22. doi:. https://pubmed.ncbi.nlm.nih.gov/20132730/

5. Shen, Wei, Zhang, Xuzhong, Tang, Min, Wang, Ying, Zhou, Haoquan. 2024. Targeting of ubiquitination and degradation of KLF15 by E3 ubiquitin ligase KBTBD7 regulates LPS-induced septic brain injury in microglia. In Experimental cell research, 443, 114317. doi:10.1016/j.yexcr.2024.114317. https://pubmed.ncbi.nlm.nih.gov/39489209/