Wu Tiantian, Zhou Hui, Wang Lulu, Tan Jianxin, Gao Wenxin, Wu Yibo, Zhao Dan, Shen Cong, Zheng Bo, Huang Xiaoyan, Shao Binbin
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, 215002, China.
Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Heliyon. 2024 Aug 23;10(17):e36744. doi: 10.1016/j.heliyon.2024.e36744. eCollection 2024 Sep 15.
Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate β-catenin signaling. Furthermore, activation of β-catenin signaling reversed the effects mediated by knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.
含三联基序蛋白59（TRIM59）是一种在多种肿瘤中发挥关键作用的生物标志物。然而，TRIM59在生殖细胞中的具体作用在很大程度上仍不清楚。在此，我们使用小鼠精原细胞系GC-1研究了TRIM59对生殖细胞的影响及其潜在调控机制。我们的结果表明，TRIM59促进GC-1细胞增殖并抑制其凋亡。机制上，TRIM59通过对AXIN1进行泛素化修饰以激活β-连环蛋白信号通路来维持GC-1细胞的行为。此外，β-连环蛋白信号通路的激活逆转了GC-1细胞中基因敲低介导的效应。总体而言，我们的研究揭示了TRIM59在GC-1细胞中的主要作用和调控机制，这为精子发生缺陷的分子发病机制提供了新的线索，并可能为男性不育的治疗提供治疗靶点。
