Trim58-KO Mouse

TRIM58, a member of the TRIM protein family, functions as an E3 ubiquitin ligase. It is involved in multiple biological processes and associated with various signaling pathways. Genome-wide association studies have implicated it in regulating human erythrocyte traits [9]. In innate immune regulation, it is a negative mediator of innate immune control and mucosal homeostasis via TLR2 signaling [3]. In the context of tumors, its role in tumorigenesis and chemoresistance is of great interest, making genetic models valuable for studying its functions.

In triple-negative breast cancer stem cells, TRIM58 down-regulation maintains stemness via the MYH9-GRK3-YAP axis activation. Overexpression of TRIM58 reduces the proportion of stem-like cells and inhibits stemness-related gene expression [1]. In breast cancer, TRIM58 promotes chemoresistance by inactivating p53/p21 via ubiquitination of DDX3 [2]. In intestinal mucosal inflammation, Trim58 -/- mice show impaired resolution of acute dextran sodium sulfate-induced colitis, indicating that TRIM58 restrains inflammation by negatively regulating TLR2 in myeloid cells [3]. In colorectal cancer, TRIM58 acts as a tumor suppressor by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway [4]. In NSCLC, TRIM58 suppresses tumor malignancy by promoting ZEB1 protein degradation via the ubiquitin-proteasome pathway [5]. In gastric cancer, TRIM58 suppresses tumor growth by inactivating β-catenin signaling via ubiquitination [6]. In osteosarcoma, TRIM58 interacts with pyruvate kinase M2 to inhibit tumorigenicity [7]. In KRAS-driven lung adenocarcinoma, TRIM58 is a prognostic biomarker remodeling the tumor microenvironment [8]. In terminal erythropoiesis, Trim58 degrades dynein and regulates the maturation of late-stage nucleated erythroblasts to anucleate reticulocytes [9].

In conclusion, TRIM58 has diverse functions in different biological processes and disease conditions. Through gene-knockout or conditional-knockout mouse models and other functional studies, it has been shown to play important roles in tumorigenesis, chemoresistance, innate immune regulation, and erythropoiesis. Understanding the functions of TRIM58 provides insights into the mechanisms of these biological processes and disease development, which may offer potential therapeutic targets.

References:

1. Li, Xujun, Jiang, Jing, Wu, Qian, You, Tianzi, Yang, Fan. 2024. TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells. In Cancer gene therapy, 31, 1186-1200. doi:10.1038/s41417-024-00780-w. https://pubmed.ncbi.nlm.nih.gov/38714850/

2. Wang, Juan, Yang, Fan, Zhuang, Jialang, Li, Jiaying, Xie, Ni. 2021. TRIM58 inactivates p53/p21 to promote chemoresistance via ubiquitination of DDX3 in breast cancer. In The international journal of biochemistry & cell biology, 143, 106140. doi:10.1016/j.biocel.2021.106140. https://pubmed.ncbi.nlm.nih.gov/34954155/

3. Eyking, Annette, Ferber, Frederike, Köhler, Stefanie, Reis, Henning, Cario, Elke. 2019. TRIM58 Restrains Intestinal Mucosal Inflammation by Negatively Regulating TLR2 in Myeloid Cells. In Journal of immunology (Baltimore, Md. : 1950), 203, 1636-1649. doi:10.4049/jimmunol.1900413. https://pubmed.ncbi.nlm.nih.gov/31383741/

4. Sun, Naizhi, Shen, Jiacheng, Shi, Yuhua, Chen, Yichuan, Sun, Jinwei. 2023. TRIM58 functions as a tumor suppressor in colorectal cancer by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway. In World journal of surgical oncology, 21, 231. doi:10.1186/s12957-023-03124-4. https://pubmed.ncbi.nlm.nih.gov/37516854/

5. Shang, Rongxin, Chen, Jiakuan, Gao, Yang, Chen, Jijun, Han, Guoliang. 2023. TRIM58 Interacts with ZEB1 to Suppress NSCLC Tumor Malignancy by Promoting ZEB1 Protein Degradation via UPP. In Disease markers, 2023, 5899662. doi:10.1155/2023/5899662. https://pubmed.ncbi.nlm.nih.gov/36644609/

6. Liu, Xiaowen, Long, Ziwen, Cai, Hong, Yu, Shengjia, Wu, Jianghong. 2019. TRIM58 suppresses the tumor growth in gastric cancer by inactivation of β-catenin signaling via ubiquitination. In Cancer biology & therapy, 21, 203-212. doi:10.1080/15384047.2019.1679554. https://pubmed.ncbi.nlm.nih.gov/31747856/

7. Yuan, Peng, Zhou, Yiyi, Wang, Rui, Liu, Yi, Yang, Huilin. 2020. TRIM58 Interacts with Pyruvate Kinase M2 to Inhibit Tumorigenicity in Human Osteosarcoma Cells. In BioMed research international, 2020, 8450606. doi:10.1155/2020/8450606. https://pubmed.ncbi.nlm.nih.gov/32219144/

8. Chen, Xiaowei, Wang, Yu, Qu, Xiao, Wang, Yadong, Du, Jiajun. 2021. TRIM58 is a prognostic biomarker remodeling the tumor microenvironment in KRAS-driven lung adenocarcinoma. In Future oncology (London, England), 17, 565-579. doi:10.2217/fon-2020-0645. https://pubmed.ncbi.nlm.nih.gov/33406903/

9. Thom, Christopher S, Traxler, Elizabeth A, Khandros, Eugene, Holzbaur, Erika L F, Weiss, Mitchell J. 2014. Trim58 degrades Dynein and regulates terminal erythropoiesis. In Developmental cell, 30, 688-700. doi:10.1016/j.devcel.2014.07.021. https://pubmed.ncbi.nlm.nih.gov/25241935/