TRIM2, also known as CMT2R or RNF86, is a member of the TRIM superfamily and functions as an E3 ubiquitin ligase. It is involved in multiple biological processes such as intracellular signaling, apoptosis, autophagy, and carcinogenesis [2]. TRIM2-related pathways include those related to p53 ubiquitination and regulation of proteins like Snail1, which are crucial for tumor-related processes [1,5].

In a Trim2A/A mouse model with a recessive null mutation of Trim2, mice develop ataxia associated with severe loss of cerebellar Purkinje cells and peripheral neuropathy, suggesting a role of TRIM2 in neuronal function [3]. Knockout of Trim2 in mice and primary fibroblasts from a Charcot-Marie-Tooth disease (CMTD) patient with TRIM2 mutations led to higher infection by New World arenaviruses, indicating its role in antiviral defense [4]. In cancer research, in CRC cells, stress-induced epinephrine promotes CRC development through the CEBPB/TRIM2/P53 axis where TRIM2 promotes p53 ubiquitination [1]. In lung adenocarcinoma, TRIM2 promotes cell proliferation, migration, and invasion by deubiquitinating and stabilizing Snail1 protein [5].

In summary, TRIM2 plays essential roles in neuroprotection, antiviral responses, and cancer-related processes. Gene-knockout mouse models have been instrumental in revealing its functions in neurological diseases, antiviral defense, and cancer, providing valuable insights into the underlying mechanisms and potential therapeutic targets for these disease areas.

References:

1. Zhou, Zili, Shu, Yan, Bao, Haijun, Jian, Chenxing, Shu, Xiaogang. 2022. Stress-induced epinephrine promotes epithelial-to-mesenchymal transition and stemness of CRC through the CEBPB/TRIM2/P53 axis. In Journal of translational medicine, 20, 262. doi:10.1186/s12967-022-03467-8. https://pubmed.ncbi.nlm.nih.gov/35672760/

2. Xiao, Maolin, Li, Jianjun, Liu, Qingyuan, Yang, Zongke, Wang, Delin. 2022. Expression and Role of TRIM2 in Human Diseases. In BioMed research international, 2022, 9430509. doi:10.1155/2022/9430509. https://pubmed.ncbi.nlm.nih.gov/36051486/

3. Li, Jian J, Sarute, Nicolas, Lancaster, Eunjoo, Ross, Susan R, Scherer, Steven S. 2020. A recessive Trim2 mutation causes an axonal neuropathy in mice. In Neurobiology of disease, 140, 104845. doi:10.1016/j.nbd.2020.104845. https://pubmed.ncbi.nlm.nih.gov/32205255/

4. Sarute, Nicolas, Ibrahim, Nouhou, Medegan Fagla, Bani, Henao-Mejia, Jorge, Ross, Susan R. 2019. TRIM2, a novel member of the antiviral family, limits New World arenavirus entry. In PLoS biology, 17, e3000137. doi:10.1371/journal.pbio.3000137. https://pubmed.ncbi.nlm.nih.gov/30726215/

5. Lin, Zhaoxian, Lin, Xing, Zhu, Lihuan, Huang, Jianyuan, Huang, Yangyun. 2020. TRIM2 directly deubiquitinates and stabilizes Snail1 protein, mediating proliferation and metastasis of lung adenocarcinoma. In Cancer cell international, 20, 228. doi:10.1186/s12935-020-01316-6. https://pubmed.ncbi.nlm.nih.gov/32536816/