TERF2, also known as Telomeric Repeat-binding Factor 2, is a crucial component of the telomere-binding protein complex. It plays a vital role in maintaining telomere stability, which is essential for chromosome integrity and cell survival. TERF2 is involved in multiple cellular processes, and its dysregulation has implications in various diseases. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying its functions [2,6].

TERF2 has been found to have diverse roles. Silencing TERF2 in cells can alter the redox status, promote the cytosolic translocation and autophagic activity of HMGB1, indicating its role in regulating autophagy [1]. In esophageal carcinoma, TERF2 is overexpressed and contributes to cell proliferation, potentially through the DDR/P53 signaling pathway [2]. In adrenocortical carcinoma, it is identified as one of the driver genes [3]. In Ph-like ALL, the novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways [4]. In sepsis-induced myocardial injury, miR-29b-1-5p exacerbates the injury by targeting TERF2 [5]. In post-hypoxic brain damages, down-regulating Terf2 in hippocampal neural cells triggers an excitotoxicity-like phenotype, while overexpressing it prevents brain damages [6].

In conclusion, TERF2 is essential for telomere stability and has far-reaching impacts on various biological processes and disease conditions. Studies using KO/CKO mouse models have been instrumental in revealing its roles in autophagy, cancer development, and neurodegenerative and cardiac diseases, providing insights into potential therapeutic targets for these diseases.

References:

1. Iachettini, Sara, Ciccarone, Fabio, Maresca, Carmen, Zizza, Pasquale, Biroccio, Annamaria. 2022. The telomeric protein TERF2/TRF2 impairs HMGB1-driven autophagy. In Autophagy, 19, 1479-1490. doi:10.1080/15548627.2022.2138687. https://pubmed.ncbi.nlm.nih.gov/36310382/

2. Yao, Lihua, Wang, Xinlu, Wang, Zihao, Wang, Xiaozhong, Guo, Xiaolan. 2024. Expression and functional analyses of TERF2 in esophageal carcinoma. In Heliyon, 10, e38040. doi:10.1016/j.heliyon.2024.e38040. https://pubmed.ncbi.nlm.nih.gov/39328506/

3. Zheng, Siyuan, Cherniack, Andrew D, Dewal, Ninad, Giordano, Thomas J, Verhaak, Roel G W. . Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. In Cancer cell, 29, 723-736. doi:10.1016/j.ccell.2016.04.002. https://pubmed.ncbi.nlm.nih.gov/27165744/

4. Xu, Guo-Fa, Zeng, Zhao, Zhang, Zhi-Bo, Liu, Yao, Chen, Su-Ning. . The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL. In Journal of cellular and molecular medicine, 28, e18114. doi:10.1111/jcmm.18114. https://pubmed.ncbi.nlm.nih.gov/38323741/

5. Jiang, Yaqing, Xu, Junmei, Zeng, Hua, Guo, Jiali, Xiao, Feng. . miR-29b-1-5p exacerbates myocardial injury induced by sepsis in a mouse model by targeting TERF2. In Acta biochimica et biophysica Sinica, 56, 607-620. doi:10.3724/abbs.2024020. https://pubmed.ncbi.nlm.nih.gov/38414350/

6. Gao, Shuaiyun, Huang, Sheng, Xu, Yiwen, Gilson, Eric, Ye, Jing. 2024. Role of the telomeric factor TRF2 in post-hypoxic brain damages. In Redox biology, 75, 103278. doi:10.1016/j.redox.2024.103278. https://pubmed.ncbi.nlm.nih.gov/39128227/