TRIM26, a member of the TRIM protein family, functions as an E3 ubiquitin ligase due to its RING structural domain [6]. It is involved in multiple biological processes such as immune response, viral invasion, and inflammatory processes, and plays roles in various diseases including malignancies and neurologic conditions [6]. Ubiquitination, in which TRIM26 is involved, is a crucial post-translational modification affecting nearly all physiological processes [6].

In glioma, TRIM26 suppresses ferroptosis by catalyzing K63-linked ubiquitination of GPX4, enhancing its stability. Its silencing impedes ferroptosis resistance and tumorigenesis [1]. In hepatocellular carcinoma, TRIM26, which is lowly expressed, inhibits cell proliferation and migration by promoting ZEB1 degradation, while USP39 acts antagonistically [2]. In non-small cell lung cancer, TRIM26 promotes cell survival by inducing PBX1 degradation [3]. In liver regeneration, Trim26 knockout mice show enhanced hepatocyte proliferation as Trim26 deficiency promotes macrophage polarization to M1 and activates the Wnt/β-catenin signaling [4]. In osteosarcoma, TRIM26 is downregulated, and overexpression inhibits cell proliferation and invasion by destabilizing RACK1 and inactivating MEK/ERK signaling [5]. In clear cell renal cell carcinoma, TRIM26 inhibits progression by destabilizing ETK and inactivating AKT/mTOR signaling [7].

In summary, TRIM26 plays diverse roles in different biological processes and diseases. Gene knockout models, such as in the case of Trim26 knockout mice in liver regeneration studies, have been crucial in revealing its functions. These studies show that TRIM26 can regulate cell death, proliferation, and metastasis in various cancers, and also affects liver regeneration, providing potential therapeutic targets for related diseases.

References:

1. Wang, Zhangjie, Xia, Yuan, Wang, Yang, Liu, Yu, Shen, Na. 2023. The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma. In Cell death & disease, 14, 695. doi:10.1038/s41419-023-06222-z. https://pubmed.ncbi.nlm.nih.gov/37872147/

2. Li, Xiaomei, Yuan, Jiahui, Song, Conghua, Wang, Weiwei, Song, Gang. 2021. Deubiquitinase USP39 and E3 ligase TRIM26 balance the level of ZEB1 ubiquitination and thereby determine the progression of hepatocellular carcinoma. In Cell death and differentiation, 28, 2315-2332. doi:10.1038/s41418-021-00754-7. https://pubmed.ncbi.nlm.nih.gov/33649471/

3. Sun, Yuening, Lin, Peng, Zhou, Xiumin, Xu, Xiaofeng, Mao, Xinliang. 2023. TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation. In International journal of biological sciences, 19, 2803-2816. doi:10.7150/ijbs.81726. https://pubmed.ncbi.nlm.nih.gov/37324936/

4. Li, Tingting, Zhong, Wei, Li, Mengqi, Luo, Fanghong, Song, Gang. 2024. TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation. In Cell death & disease, 15, 453. doi:10.1038/s41419-024-06798-0. https://pubmed.ncbi.nlm.nih.gov/38926362/

5. Xia, Kezhou, Zheng, Di, Wei, Zhun, Liu, Wenda, Guo, Weichun. 2023. TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. In Cell death & disease, 14, 529. doi:10.1038/s41419-023-06048-9. https://pubmed.ncbi.nlm.nih.gov/37591850/

6. Zou, Jialai, Niu, Kaiyi, Lu, Tao, Cheng, Hao, Xu, Lijian. . The Multifunction of TRIM26: From Immune Regulation to Oncology. In Protein and peptide letters, 31, 424-436. doi:10.2174/0109298665311516240621114519. https://pubmed.ncbi.nlm.nih.gov/38956921/

7. Zheng, Di, Ning, Jinzhuo, Deng, Hao, Ruan, Yuan, Cheng, Fan. 2024. TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling. In Journal of translational medicine, 22, 481. doi:10.1186/s12967-024-05273-w. https://pubmed.ncbi.nlm.nih.gov/38773612/