TRIM56, a member of the TRIM (tripartite motif) protein family, can function as an E3 ubiquitin ligase and has deubiquitinase activity as well as the ability to bind RNA [2]. It is involved in multiple biological pathways, such as innate immune response including TLR and cGAS-STING pathways, and plays roles in processes like lipid metabolism, antiviral defense, and tumorigenesis [2,3,4,5,6,7,8]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In the context of non-alcoholic fatty liver disease (NAFLD), hepatocyte-specific ablation of TRIM56 exacerbated the disease progression, while hepatic TRIM56 overexpression suppressed it. TRIM56 was found to directly interact with fatty acid synthase (FASN), a lipogenesis factor, and trigger its K48-linked ubiquitination-dependent degradation, indicating its role in lipid metabolism [1]. In glioblastoma, elevated TRIM56 expression promoted glioma progression in vitro and in xenograft models. TRIM56 deubiquitinated cIAP1, reducing its degradation, and also regulated post-translational modifications to contribute to glioma development through cIAP1 stabilization [4].

In conclusion, TRIM56 is crucial in various biological processes. Through model-based research, especially KO/CKO mouse models, its role in diseases like NAFLD and glioblastoma has been revealed. It plays important roles in lipid metabolism, antiviral innate immunity, and tumorigenesis, providing potential therapeutic targets for these disease areas.

References:

1. Xu, Suowen, Wu, Xiumei, Wang, Sichen, Ji, Yan-Xiao, Weng, Jianping. 2024. TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase. In The Journal of clinical investigation, 134, . doi:10.1172/JCI166149. https://pubmed.ncbi.nlm.nih.gov/38206764/

2. Fu, Lin, Zhou, Xiaotong, Jiao, Qian, Chen, Xi. 2023. The Functions of TRIM56 in Antiviral Innate Immunity and Tumorigenesis. In International journal of molecular sciences, 24, . doi:10.3390/ijms24055046. https://pubmed.ncbi.nlm.nih.gov/36902478/

3. Zhang, Weifeng, Li, Gaocai, Zhou, Xingyu, Zhao, Kangcheng, Yang, Cao. 2024. Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration. In The Journal of clinical investigation, 134, . doi:10.1172/JCI165140. https://pubmed.ncbi.nlm.nih.gov/38488012/

4. Yang, Xu, Zhang, Yan, Xue, Zhiwei, Han, Mingzhi, Wang, Jian. 2022. TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein. In Journal of experimental & clinical cancer research : CR, 41, 336. doi:10.1186/s13046-022-02534-8. https://pubmed.ncbi.nlm.nih.gov/36471347/

5. Zhang, Qing, Zheng, Jianglin, Wu, Wenjie, Wang, Xuan, Jiang, Xiaobing. 2023. TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion. In Cell death & disease, 14, 178. doi:10.1038/s41419-023-05702-6. https://pubmed.ncbi.nlm.nih.gov/36870986/

6. Wang, Yao, Dong, Yanyan, Luan, Tian, Zhong, Zhaohua, Zhao, Wenran. 2024. TRIM56 restricts Coxsackievirus B infection by mediating the ubiquitination of viral RNA-dependent RNA polymerase 3D. In PLoS pathogens, 20, e1012594. doi:10.1371/journal.ppat.1012594. https://pubmed.ncbi.nlm.nih.gov/39348396/

7. Wang, Dang, Li, Kui. 2025. Emerging Roles of TRIM56 in Antiviral Innate Immunity. In Viruses, 17, . doi:10.3390/v17010072. https://pubmed.ncbi.nlm.nih.gov/39861861/

8. Tian, Xing, Dong, Huijun, Lai, Xinyuan, Li, Tong, Xiang, Kuanhui. 2022. TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity. In Antiviral research, 207, 105406. doi:10.1016/j.antiviral.2022.105406. https://pubmed.ncbi.nlm.nih.gov/36084850/