Trim35, a member of the tripartite motif (TRIM) family, functions as an E3 ubiquitin ligase. It is involved in multiple biological pathways, such as innate immunity, cell growth regulation, and metabolism [1,3]. In innate immunity, it plays a role in the RIG-I antiviral immunity pathway, and also impacts the cGAS-STING-mediated antiviral response [1,4]. Genetic models like KO/CKO mouse models are valuable for studying its functions.

In Trim35-deficient mice, the production of type I interferon in response to viral infection is suppressed, making them more susceptible to influenza A virus infection, which reveals Trim35's role in innate antiviral immune response [1]. In fibroblast-specific Trim35 gene knockout (Trim35cKO) mice, cardiac fibrosis and hypertrophy are significantly improved, indicating that TRIM35 in fibroblasts plays a role in cardiac remodeling [3]. In cardiomyocyte-specific Trim35 overexpression transgenic mice, increased P53 transcriptional activity is sufficient to initiate heart failure, suggesting TRIM35's role in heart failure pathogenesis.

In summary, Trim35 is crucial in innate immunity, cardiac-related processes and potentially in cancer. Mouse models, including KO/CKO models, have been instrumental in uncovering its roles in antiviral defense, cardiac remodeling and heart failure, providing insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Sun, Nan, Jiang, Li, Ye, Miaomiao, Chen, Hualan, Li, Chengjun. 2020. TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2. In Protein & cell, 11, 894-914. doi:10.1007/s13238-020-00734-6. https://pubmed.ncbi.nlm.nih.gov/32562145/

2. Lorenzana-Carrillo, Maria Areli, Tejay, Saymon, Nanoa, Joseph, Michelakis, Evangelos D, Sutendra, Gopinath. 2024. TRIM35 Monoubiquitinates H2B in Cardiac Cells, Implications for Heart Failure. In Circulation research, 135, 301-313. doi:10.1161/CIRCRESAHA.123.324202. https://pubmed.ncbi.nlm.nih.gov/38860363/

3. Yang, Boshen, Wang, Zhixiang, Niu, Kaifan, Song, Juan, Lu, Xia. 2024. TRIM35 triggers cardiac remodeling by regulating SLC7A5-mediated amino acid transport and mTORC1 activation in fibroblasts. In Cell communication and signaling : CCS, 22, 444. doi:10.1186/s12964-024-01826-0. https://pubmed.ncbi.nlm.nih.gov/39304904/

4. Zhang, Jikai, Wu, Yuhao, Wang, Yiwen, Qin, Baoying, Sun, Nan. 2024. TRIM35 Negatively Regulates the cGAS-STING-Mediated Signaling Pathway by Attenuating K63-Linked Ubiquitination of STING. In Inflammation, 48, 855-869. doi:10.1007/s10753-024-02093-4. https://pubmed.ncbi.nlm.nih.gov/39088122/