TRIM26, a member of the TRIM family, functions as an E3 ubiquitin ligase due to its RING structural domain [6,7]. It is involved in diverse biological processes such as immune response, viral invasion, and inflammatory processes, and contributes to the progression of various diseases including malignancies and neurologic conditions [6].

In glioma, TRIM26 promotes K63-linked ubiquitination of GPX4, enhancing its stability and suppressing ferroptosis. Silencing TRIM26 impedes ferroptosis resistance and tumorigenesis [1]. In hepatocellular carcinoma, TRIM26, in an antagonistic pattern with USP39, promotes ZEB1 degradation, thus inhibiting cell proliferation and migration [2]. In non-small cell lung cancer, TRIM26 binds to PBX1, mediates its K48-linked polyubiquitination and proteasomal degradation, promoting cancer cell survival [3]. In liver regeneration, Trim26 knockout mice show enhanced hepatocyte proliferation. Trim26 deficiency promotes macrophage polarization to M1 phenotype and activates 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 binds to ETK, facilitating its ubiquitination and degradation, and inactivating AKT/mTOR signaling to inhibit cancer progression [8].

In summary, TRIM26 plays crucial roles in multiple biological processes and diseases. Gene knockout models, especially in mice, have been instrumental in revealing its functions in cancer, liver regeneration, and immune-related processes. Understanding TRIM26 can potentially lead to new therapeutic strategies for these disease areas.

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. Sharma, Mona, Liu, Ke, Wei, Jianchao, Ma, Zhiyong, Qiu, Yafeng. 2024. Mechanistic Role of TRIM26 in Viral Infection and Host Defense. In Genes, 15, . doi:10.3390/genes15111476. https://pubmed.ncbi.nlm.nih.gov/39596676/

8. 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/