Henan Key Laboratory of Precision Clinical Pharmacy, Academy of Medical Sciences, Zhengzhou University, Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Int J Biol Macromol. 2024 Jan;254(Pt 3):126801. doi: 10.1016/j.ijbiomac.2023.126801. Epub 2023 Sep 7.
Histone lysine-specific demethylase 1 (LSD1) expression has been evaluated in multiple tumors, including gastric cancer (GC). However, the mechanisms underlying LSD1 dysregulation in GC remain largely unclear. In this study, neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) was identified to be conjugated to LSD1 at K63 by ubiquitin-conjugating enzyme E2 M (UBE2M), and this neddylated LSD1 could promote LSD1 ubiquitination and degradation, leading to a decrease of GC cell stemness and chemoresistance. Herein, our findings revealed a novel mechanism of LSD1 neddylation and its contribution to decreasing GC cell stemness and chemoresistance. Taken together, our findings may whistle about the future application of neddylation inhibitors.
组蛋白赖氨酸特异性去甲基化酶 1（LSD1）的表达已在多种肿瘤中进行了评估，包括胃癌（GC）。然而，GC 中 LSD1 失调的机制在很大程度上仍不清楚。在这项研究中，鉴定出神经前体细胞表达的发育下调蛋白 8（NEDD8）通过泛素结合酶 E2 M（UBE2M）与 LSD1 的赖氨酸 63 位结合，这种连接有 NEDD8 的 LSD1 可以促进 LSD1 的泛素化和降解，从而降低 GC 细胞的干性和化疗耐药性。在此，我们的研究结果揭示了 LSD1 连接 NEDD8 的新机制及其对降低 GC 细胞干性和化疗耐药性的贡献。总之，我们的研究结果可能预示着 NEDD8 抑制剂的未来应用。
