Trim27, also known as RFP, is a RING-mediated E3 ubiquitin ligase. It can mark other proteins like PTEN, IκBα and p53 for degradation, regulating multiple signaling pathways and biological processes such as cell proliferation, differentiation, and apoptosis [3]. It is involved in pathways like Wnt/β-catenin, autophagy-related pathways, and endosomal trafficking regulation.

Knockout of Trim27 in mice causes IBS-like symptoms, including increased visceral hyperalgesia and abnormal stool features, revealing its crucial role in maintaining gut homeostasis by stabilizing β-catenin and activating Wnt/β-catenin signaling for intestinal stem cell self-renewal [1]. In tuberculosis, Trim27-deficient mice show decreased autophagy-related gene transcription and attenuated autophagy flux, indicating its role in enhancing host macroautophagy/autophagy flux against Mycobacterium tuberculosis [2]. In cancer-related studies, Trim27 knockout in mouse models shows increased basal autophagy levels and differential regulation of tumorigenesis and metastasis, suggesting its role in negatively controlling autophagy in human breast cancer [4].

In conclusion, Trim27 is essential for maintaining gut homeostasis and host immunity against tuberculosis, and is involved in the regulation of autophagy and tumorigenesis. Gene knockout mouse models have significantly contributed to understanding its roles in IBS, tuberculosis, and cancer, providing potential therapeutic targets for these diseases.

References:

1. Wang, Jing, Zhao, Dongdong, Lei, Zehui, Zhang, Lingqiang, Liu, Cui Hua. 2023. TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal. In Cellular & molecular immunology, 20, 158-174. doi:10.1038/s41423-022-00963-1. https://pubmed.ncbi.nlm.nih.gov/36596873/

2. Zhao, Dongdong, Qiang, Lihua, Lei, Zehui, Liu, Cui Hua, Wang, Jing. 2024. TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux. In Autophagy, 20, 1483-1504. doi:10.1080/15548627.2024.2321831. https://pubmed.ncbi.nlm.nih.gov/38390831/

3. Yu, Chengpeng, Rao, Dean, Wang, Tiantian, Zhang, Lei, Huang, Wenjie. 2022. Emerging roles of TRIM27 in cancer and other human diseases. In Frontiers in cell and developmental biology, 10, 1004429. doi:10.3389/fcell.2022.1004429. https://pubmed.ncbi.nlm.nih.gov/36200036/

4. Yang, Yi, Zhu, Yifu, Zhou, Shuai, Wu, Mian, Chen, Song. 2022. TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis. In The EMBO journal, 41, e109777. doi:10.15252/embj.2021109777. https://pubmed.ncbi.nlm.nih.gov/35670107/