TRIM50, a member of the tripartite motif family, has diverse functions. It is involved in multiple biological processes, including the regulation of autophagy, inflammasome activation, and vesicular trafficking [1,6,9]. In the ubiquitin-proteasome system, it functions as an E3 ubiquitin ligase, which is crucial for the ubiquitination of various proteins, thus regulating different cellular pathways [2,3,4,5,7,8].

In in vivo studies, TRIM50-overexpressing mice showed NLRP3 inflammasome-mediated diseases, indicating its role in promoting NLRP3 inflammasome activation through direct NLRP3 oligomerization [1]. In gastric cancer, TRIM50 knockdown led to increased cell proliferation, invasion, and migration, while overexpression had the opposite effects, suggesting its role as a tumor suppressor [2,3,4]. Similar tumor-suppressive effects were seen in ovarian, pancreatic, and hepatocarcinoma models [5,7,8]. For example, in pancreatic cancer, TRIM50 overexpression decreased cell proliferation and motility, reversing the epithelial-mesenchymal transition by degrading Snail1 [7].

In conclusion, TRIM50 plays essential roles in regulating autophagy, inflammasome activation, and tumorigenesis. The use of gene knockout or overexpression models in mice has been instrumental in revealing its functions in NLRP3-related diseases and various cancers, providing potential therapeutic targets for these conditions.

References:

1. Lin, Yueke, Lv, Xiaoting, Sun, Caiyu, Xuan, Haocheng, Han, Lihui. 2022. TRIM50 promotes NLRP3 inflammasome activation by directly inducing NLRP3 oligomerization. In EMBO reports, 23, e54569. doi:10.15252/embr.202154569. https://pubmed.ncbi.nlm.nih.gov/36178239/

2. Gu, Chao, Xia, Yiwen, Lu, Chen, Xu, Zekuan, Li, Bowen. 2024. TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1. In International journal of biological sciences, 20, 3656-3674. doi:10.7150/ijbs.97091. https://pubmed.ncbi.nlm.nih.gov/38993561/

3. Li, Rongzhou, Xu, Peng, Jin, Xiaosheng, Yu, Weilai, Ji, Tingting. 2022. TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation. In Journal of oncology, 2022, 5936753. doi:10.1155/2022/5936753. https://pubmed.ncbi.nlm.nih.gov/36046365/

4. Hu, Jiajia, Huang, Runjie, Liang, Chengcai, Wang, Feng, Yuan, Shuqiang. . TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP. In Molecular cancer research : MCR, 21, 1107-1119. doi:10.1158/1541-7786.MCR-23-0113. https://pubmed.ncbi.nlm.nih.gov/37409971/

5. Qiu, Yumin, Liu, Peishu, Ma, Xiaomin, Shi, Juanjuan, Han, Lihui. 2019. TRIM50 acts as a novel Src suppressor and inhibits ovarian cancer progression. In Biochimica et biophysica acta. Molecular cell research, 1866, 1412-1420. doi:10.1016/j.bbamcr.2019.06.002. https://pubmed.ncbi.nlm.nih.gov/31176697/

6. Fusco, Carmela, Mandriani, Barbara, Di Rienzo, Martina, Fimia, Gian Maria, Merla, Giuseppe. 2018. TRIM50 regulates Beclin 1 proautophagic activity. In Biochimica et biophysica acta. Molecular cell research, 1865, 908-919. doi:10.1016/j.bbamcr.2018.03.011. https://pubmed.ncbi.nlm.nih.gov/29604308/

7. Li, Rongkun, Zhu, Lili, Peng, Yangxizi, Dai, Chunhua, Liu, Dejun. 2021. TRIM50 Suppresses Pancreatic Cancer Progression and Reverses the Epithelial-Mesenchymal Transition via Facilitating the Ubiquitous Degradation of Snail1. In Frontiers in oncology, 11, 695740. doi:10.3389/fonc.2021.695740. https://pubmed.ncbi.nlm.nih.gov/34568024/

8. Ma, Xiaoxiao, Ma, Xiaomin, Qiu, Yumin, Sun, Yanlin, Han, Lihui. 2018. TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation. In Cell death & disease, 9, 608. doi:10.1038/s41419-018-0644-4. https://pubmed.ncbi.nlm.nih.gov/29789583/

9. Nishi, Miyuki, Aoyama, Fumiyo, Kisa, Fumihiko, Sawaguchi, Akira, Takeshima, Hiroshi. 2012. TRIM50 protein regulates vesicular trafficking for acid secretion in gastric parietal cells. In The Journal of biological chemistry, 287, 33523-32. doi:. https://pubmed.ncbi.nlm.nih.gov/22872646/