The oxidative modification of transcription factor FOXM1 by Peroxiredoxin1 facilitates DNA damage repair and cancer progression.

The oxidative modification of proteins induced by hydrogen peroxide (H2O2) results in the formation of disulfide bond between two cysteines and affects protein conformation and biological function. Transcription factor FOXM1 participates in the development and progression of cancers and its levels are upregulated by the oxidative stress of H2O2-treated condition. In this study, we found that Peroxiredoxin-1 (PRDX1), one of the most H2O2-reactive antioxidant enzymes, interacted with FOXM1 and led to its oxidation under H2O2 stimulation through generating an intermolecular disulfide bond with FOXM1 C539, which was subsequently transferred to form an intramolecular disulfide bond between C167 and C175 in the oxidized FOXM1. The PRDX1-mediated oxidative modification enhanced the protein stability and transcriptional activity of FOXM1, which stimulated the transcription of FOXM1 target gene X-ray cross-complementing protein 1 (XRCC1) and improved the repair of H2O2-induced DNA damage in cancer cells. The disruption of PRDX1-mediated FOXM1 oxidation impaired the colony formation ability of cancer cells in vitro and the growth and DNA damage repair ability of cancer cells in vivo. The analysis of The Cancer Genome Atlas (TCGA) breast cancer patient data confirmed that PRDX1 and FOXM1 together facilitated clinical cancer progression. Overall, we established an H2O2-PRDX1-FOXM1 oxidation pathway that likely contribute to the development and progression of cancers.

• Publication year

  2025

• Venue

  American Journal of Cancer Research

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.62347/opfs8189PMID 41244121PMCID PMC12616168
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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