Keap1-Nrf2 regulatory system and cancer

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Nrf2 is a transcription factor belonging to the Cap'n'collar (CNC) family that contains four members: Nrf1, Nrf2, Nrf3, and p45 NF-E2. Nrf2 forms a heterodimer with small Maf (sMaf) protein and binds to antioxidative/electrophile responsive element (ARE/EpRE). Nrf2 coordinately regulates many cytoprotective enzyme genes, which products are responsible for detoxification, antioxidative stress response, drug transport, and metabolism. In normal conditions, Nrf2 binds to Keap1, an adaptor protein of Cullin3 (Cul3)-based ubiquitin E3 ligase, and is degraded through the proteasome pathway. NRF2 is activated in a variety of human cancers through disrupted binding of KEAP1 and NRF2. The disruption of KEAP- NRF2 interaction in cancer cells include a number of unique mechanisms; for instance, somatic mutations in KEAP1 or NRF2 genes, aberrant accumulation of molecular chaperone p62, modification of cysteine residues by onco-metabolites, or downregulation of KEAP1 gene expression by methylation of the promoter. Eventual activation of NRF2 confers radio-chemoresistance on cancer cells and helps them to proliferate and to acquire malignancy. NRF2 has emerged as an important molecular target of anti-cancer drugs.

Original languageEnglish
Title of host publicationProtein Modifications in Pathogenic Dysregulation of Signaling
PublisherSpringer Japan
Pages269-285
Number of pages17
ISBN (Electronic)9784431555612
ISBN (Print)9784431555605
DOIs
Publication statusPublished - 2015 Sep 2

Keywords

  • Cancer
  • Chemical carcinogen
  • Keap1
  • Nrf2
  • Nrf2 inducer
  • Pten
  • Ubiquitin-proteasome pathway

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Taguchi, K., & Yamamoto, M. (2015). Keap1-Nrf2 regulatory system and cancer. In Protein Modifications in Pathogenic Dysregulation of Signaling (pp. 269-285). Springer Japan. https://doi.org/10.1007/978-4-431-55561-2_17