Elob-KO Mouse

Elob, also known as Elongin B, is a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex. It plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Elob, as part of the Elongin complex, is also involved in RNA polymerase II transcription regulation [2,4].

Blocking the BC-box-binding pocket of the Elongin BC (ELOB/C) dimer with a designed peptide can decrease cancer cell viability, increase apoptosis, and perturb gene expression, suggesting a potential strategy to inhibit cancer cell growth [1]. In breast cancer, down-regulation of ELOB significantly suppresses the proliferation of breast cancer cells both in vivo and in vitro by regulating the ubiquitination and degradation of oncoprotein p14/ARF [2]. In triple-negative breast cancer, high ELOB expression is associated with poor prognosis in radiotherapy-treated patients, and targeting ELOB can enhance radiosensitivity by modulating mitochondrial function [3]. In male infertility, Asb1 knockout mice with excessive oxidative stress and decreased H2S levels in testes show that ASB1 interacts with ELOB to enhance the K48-linked ubiquitination of sulfide-quinone oxidoreductase (SQOR), leading to its proteasomal degradation, which is crucial for H2S homeostasis and redox balance [5].

In conclusion, Elob is crucial in processes like ubiquitination-mediated protein degradation, transcription regulation, and has implications in cancer and male infertility. The studies using in vivo models such as cancer cell-based in vivo experiments and knockout mouse models have revealed its role in these disease-related biological processes, offering potential therapeutic targets for related diseases.

References:

1. Fischer, Sabrina, Trinh, Van Tuan, Simon, Clara, Liefke, Robert, Vázquez, Olalla. 2023. Peptide-mediated inhibition of the transcriptional regulator Elongin BC induces apoptosis in cancer cells. In Cell chemical biology, 30, 766-779.e11. doi:10.1016/j.chembiol.2023.05.012. https://pubmed.ncbi.nlm.nih.gov/37354906/

2. Sui, Xin-Yi, Ma, Xiao-Yan, Hou, Yujin, Shao, Zhi-Ming, Zhang, Wen-Juan. 2024. Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF. In Cell biology and toxicology, 40, 24. doi:10.1007/s10565-024-09864-7. https://pubmed.ncbi.nlm.nih.gov/38653919/

3. Li, Guo, Lin, Xinyue, Wang, Xinpeng, Zhu, Yunyun, Fu, Zhichao. 2024. Enhancing radiosensitivity in triple-negative breast cancer through targeting ELOB. In Breast cancer (Tokyo, Japan), 31, 426-439. doi:10.1007/s12282-024-01554-w. https://pubmed.ncbi.nlm.nih.gov/38472737/

4. Chen, Ying, Kokic, Goran, Dienemann, Christian, Urlaub, Henning, Cramer, Patrick. 2023. Structure of the transcribing RNA polymerase II-Elongin complex. In Nature structural & molecular biology, 30, 1925-1935. doi:10.1038/s41594-023-01138-w. https://pubmed.ncbi.nlm.nih.gov/37932450/

5. Lv, Jinxing, Wu, Tiantian, Xue, Jiajia, Huang, Xiaoyan, Zheng, Bo. 2024. ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis. In Redox biology, 79, 103484. doi:10.1016/j.redox.2024.103484. https://pubmed.ncbi.nlm.nih.gov/39733518/