TRIM25, a tripartite motif-containing protein, functions as an E3 ubiquitin ligase and is involved in multiple biological pathways. It plays a crucial role in the antiviral innate immune response, especially in the activation of the RIG-I signaling pathway. Additionally, it is associated with processes like cell proliferation and endoplasmic reticulum (ER) homeostasis, thus having overall biological importance. Genetic models, such as KO/CKO mouse models, can be valuable in further elucidating its functions [4,5,6].

In hepatocellular carcinoma, depletion of TRIM25 leads to ER stress and attenuates tumor cell growth in vitro and in vivo. Mechanistically, TRIM25 promotes cell survival and growth by targeting Keap1 for ubiquitination and degradation, activating Nrf2 [1]. In breast cancer, its regulation and function suggest it may be a biomarker and therapeutic target, as estrogens modulate its gene expression, and it has E3-ligase activity for ubiquitin and interferon-stimulated gene 15 protein [2]. In antiviral defense, TRIM25 is a marker of antiviral stress granules, and its co-condensation with G3BP1 enhances its ubiquitination activity towards antiviral proteins, activating the RIG-I signaling pathway to restrain RNA virus infection [3].

In summary, TRIM25 is essential in antiviral innate immunity, cell survival, and growth processes. Model-based research, especially through KO/CKO mouse models, has revealed its role in cancer development and antiviral responses, providing potential targets for tumor therapy and a better understanding of antiviral mechanisms.

References:

1. Liu, Yanfeng, Tao, Shishi, Liao, Lijuan, Yang, Xiaolu, Chen, Liang. 2020. TRIM25 promotes the cell survival and growth of hepatocellular carcinoma through targeting Keap1-Nrf2 pathway. In Nature communications, 11, 348. doi:10.1038/s41467-019-14190-2. https://pubmed.ncbi.nlm.nih.gov/31953436/

2. Tecalco-Cruz, Angeles C, Abraham-Juárez, María Jazmin, Solleiro-Villavicencio, Helena, Ramírez-Jarquín, Josué Orlando. . TRIM25: A central factor in breast cancer. In World journal of clinical oncology, 12, 646-655. doi:10.5306/wjco.v12.i8.646. https://pubmed.ncbi.nlm.nih.gov/34513598/

3. Shang, Zehua, Zhang, Sitao, Wang, Jinrui, Bai, Peng, Jia, Da. 2024. TRIM25 predominately associates with anti-viral stress granules. In Nature communications, 15, 4127. doi:10.1038/s41467-024-48596-4. https://pubmed.ncbi.nlm.nih.gov/38750080/

4. Choudhury, Nila Roy, Heikel, Gregory, Michlewski, Gracjan. 2020. TRIM25 and its emerging RNA-binding roles in antiviral defense. In Wiley interdisciplinary reviews. RNA, 11, e1588. doi:10.1002/wrna.1588. https://pubmed.ncbi.nlm.nih.gov/31990130/

5. Rahimi-Tesiye, Maryam, Zaersabet, Mona, Salehiyeh, Sajad, Jafari, Seyedeh Zahra. 2023. The role of TRIM25 in the occurrence and development of cancers and inflammatory diseases. In Biochimica et biophysica acta. Reviews on cancer, 1878, 188954. doi:10.1016/j.bbcan.2023.188954. https://pubmed.ncbi.nlm.nih.gov/37437700/

6. Gack, Michaela U, Shin, Young C, Joo, Chul-Hyun, Inoue, Satoshi, Jung, Jae U. . TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. In Nature, 446, 916-920. doi:. https://pubmed.ncbi.nlm.nih.gov/17392790/