TRIM47, a member of the tripartite motif-containing protein family, functions as an E3 ubiquitin ligase. It is involved in multiple biological pathways such as NF-κB, MAPK, and those related to ubiquitination, playing a significant role in processes like inflammation, cell death, and cancer progression. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying TRIM47's functions.

In LPS-induced acute lung injury, TRIM47-deficient mice showed resistance as TRIM47 promotes pulmonary inflammation by enhancing K63-linked ubiquitination of TRAF2, activating NF-κB and MAPK signaling pathways [1]. In hepatocellular carcinoma, knockdown of TRIM47 induced ferroptosis through the CDO1-mediated regulation of GSH synthesis [2]. In hematopoietic stem cells, Trim47 deficiency impaired their function and survival after stress, as Trim47 negatively regulates the MAVS-mediated innate immune pathway via K48-linked ubiquitination and degradation of MAVS [3].

Overall, TRIM47 is crucial in inflammation-related diseases like acute lung injury and in cancer progression, including hepatocellular carcinoma, gastric cancer, prostate cancer, and ovarian cancer. The KO/CKO mouse models have been instrumental in revealing these functions, highlighting TRIM47 as a potential therapeutic target in these disease areas.

References:

1. Qian, Yisong, Wang, Ziwei, Lin, Hongru, Fu, Mingui, Xin, Hong-Bo. 2022. TRIM47 is a novel endothelial activation factor that aggravates lipopolysaccharide-induced acute lung injury in mice via K63-linked ubiquitination of TRAF2. In Signal transduction and targeted therapy, 7, 148. doi:10.1038/s41392-022-00953-9. https://pubmed.ncbi.nlm.nih.gov/35513381/

2. Zhang, Jie, Yimamu, Malire, Cheng, Ziqi, Wu, Jianye, Guo, Chuanyong. 2024. TRIM47-CDO1 axis dictates hepatocellular carcinoma progression by modulating ferroptotic cell death through the ubiquitin‒proteasome system. In Free radical biology & medicine, 219, 31-48. doi:10.1016/j.freeradbiomed.2024.04.222. https://pubmed.ncbi.nlm.nih.gov/38614226/

3. Chen, Fang, Lu, Yukai, Xu, Yang, Hu, Mengjia, Wang, Junping. 2024. Trim47 prevents hematopoietic stem cell exhaustion during stress by regulating MAVS-mediated innate immune pathway. In Nature communications, 15, 6787. doi:10.1038/s41467-024-51199-8. https://pubmed.ncbi.nlm.nih.gov/39117713/