Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 254, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2023.126801
Keywords
China; LSD1; Neddylation; UBE2M; Stemness; Gastric cancer
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This study identifies the conjugation of NEDD8 to LSD1 and its impact on GC cells, revealing the significance of LSD1 neddylation in GC.
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 ned-dylation inhibitors.
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