Trim17-KO Mouse

TRIM17, a member of the TRIM family, is a RING-containing E3 ubiquitin-ligase. It has a low expression level in most adult tissues except testis and some brain regions, but can be highly induced under stress conditions, acting as a potential stress sensor. It is involved in multiple cellular processes such as apoptosis, autophagy, and cell division, and is also associated with pathological conditions like Parkinson's disease and cancer [1].

In cancer research, knockdown experiments have shown its significance. In gastric cancer, TRIM17 promotes cell survival and progression by interacting with BAX, promoting its ubiquitination and proteasomal degradation, thus antagonizing apoptosis. High TRIM17 levels in human gastric cancer specimens indicate poor survival for patients [2]. In non-small cell lung cancer, knockdown of TRIM17 increases the sensitivity of NSCLC cells to cisplatin both in vitro and in vivo, as TRIM17-mediated cisplatin resistance is related to the ubiquitination and degradation of RBM38 [3]. In neurons, Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis. Knock-down of Trim17 expression reduces both ubiquitination and degradation of Mcl-1 in neurons [4].

In conclusion, TRIM17 plays essential roles in various cellular processes and disease conditions. Model-based research, especially loss-of-function experiments, has revealed its significance in cancer and neuronal apoptosis. These findings provide potential therapeutic targets and insights into disease mechanisms for conditions such as gastric cancer, non-small cell lung cancer, and Parkinson's disease.

References:

1. Basu-Shrivastava, Meenakshi, Kozoriz, Alina, Desagher, Solange, Lassot, Iréna. 2021. To Ubiquitinate or Not to Ubiquitinate: TRIM17 in Cell Life and Death. In Cells, 10, . doi:10.3390/cells10051235. https://pubmed.ncbi.nlm.nih.gov/34069831/

2. Shen, Jiajia, Yang, Hang, Qiao, Xinran, Yu, Qiang, Wang, Zhen. 2023. The E3 ubiquitin ligase TRIM17 promotes gastric cancer survival and progression via controlling BAX stability and antagonizing apoptosis. In Cell death and differentiation, 30, 2322-2335. doi:10.1038/s41418-023-01221-1. https://pubmed.ncbi.nlm.nih.gov/37697039/

3. Zhong, Tian, Zhang, Jing, Liu, Xingren, Li, Hongmin. 2023. TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer. In Cellular oncology (Dordrecht, Netherlands), 46, 1493-1507. doi:10.1007/s13402-023-00825-6. https://pubmed.ncbi.nlm.nih.gov/37219768/

4. Magiera, M M, Mora, S, Mojsa, B, Lassot, I, Desagher, S. 2012. Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons. In Cell death and differentiation, 20, 281-92. doi:10.1038/cdd.2012.124. https://pubmed.ncbi.nlm.nih.gov/22976837/