Post-translational modification of Keap1 regulates oxidative stress-related diseases

doi:10.16352/j.issn.1001-6325.2025.01.0107

Abstract

Abstract: The activation of Keap1-Nrf2 signaling pathway is an important mechanism for cells to resist oxidative stress. Under oxidative stress, Keap1 is affected by post-translational modification(PTM) such as glutathione, alkylation and S-sulfhydrylation, which weakens its binding to Nrf2, leading to Nrf2 accumulation, nuclear translocation and the expression and transcription of downstream detoxification and antioxidant defense proteins. The PTM of Keap1 is involved in the regulation of a variety of oxidative stress-related diseases such as cancer, Parkinson′s disease and atherosclerosis. For example, alkylation inhibits abdominal aortic aneurysm formation, methylation promotes innate resistance of breast cancer, and S-sulfhydrylation improves atherosclerosis, which provides a theoretical basis for finding new drug targets and biomarkers.

Key words: Keap1, oxidative stress, post-translational modifications, mechanism of action

CLC Number:

R966

QU Ying, MAO Caiyun, ZHONG Qing, ZHANG Rong, SONG Yunjia. Post-translational modification of Keap1 regulates oxidative stress-related diseases[J]. Basic & Clinical Medicine, 2025, 45(1): 107-111.

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