PRDX1 inhibits ferroptosis by binding to Cullin-3 as a molecular chaperone in colorectal cancer.

ABSTRACT: Peroxiredoxin 1 (PRDX1) is a potent antioxidant protein that displays a unique molecular chaperone activity. However, the role of overexpression of PRDX1 in colorectal cancer (CRC) was elusive. Herein, we found that the number of AOM/DSS-induced colitis-associated CRC in PRDX1 knockout mice was significantly lower than that in wild-type mice, concomitant with the downregulation of NRF2 and GPX4. Mechanistically, RNA sequencing results indicated that knockdown of PRDX1 resulted in a significant reduction of NRF2, which further triggered ROS-induced mitochondrial dysfunction and lipid peroxidation-induced ferroptosis in CRC cells. Notably, PRDX1 inhibited NRF2 degradation and promoted NRF2 nuclear translocation, thereby triggering the transcription of GPX4. Immunoprecipitation-mass spectrome

SUBMITTER: Song Y 

PROVIDER: S-EPMC11489176 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature