Regulatory mechanisms of cellular response to oxidative stress

Ken Itoh, Tetsuro Ishii, Nobunao Wakabayashi, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

296 Citations (Scopus)


An antioxidant responsive element (ARE) or electrophile responsive element (EpRE) mediates the transcriptional activation of genes encoding phase II drug metabolizing enzymes. The ARE consensus sequence shows high similarity to an erythroid gene regulatory element, and based on the observation, we have recently found that transcription factor Nrf2 is essential for the coordinate induction of phase II detoxifying enzymes. The expression of anti-oxidative stress enzyme genes is also regulated by Nrf2. Detailed analysis of the regulatory mechanisms of Nrf2 activity has ultimately led us to the identification of a new protein, which we have named Keap1, that suppresses Nrf2 activity by specific binding to its evolutionarily-conserved N-terminal Neh2 regulatory domain.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalFree Radical Research
Issue number4
Publication statusPublished - 1999 Oct 6
Externally publishedYes


  • ARE
  • EpRE
  • Nrf2
  • Phase II enzyme

ASJC Scopus subject areas

  • Biochemistry


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