Keap1-Nrf2 regulatory system and cancer

研究成果: Chapter

1 被引用数 (Scopus)

抄録

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.

本文言語English
ホスト出版物のタイトルProtein Modifications in Pathogenic Dysregulation of Signaling
出版社Springer Japan
ページ269-285
ページ数17
ISBN(電子版)9784431555612
ISBN(印刷版)9784431555605
DOI
出版ステータスPublished - 2015 9 2

ASJC Scopus subject areas

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

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