Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain

Wenge Li, Si Wang Yu, A. N.Tony Kong

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

NF-E2-related factor 2 (Nrf2) is the key transcription factor regulating the antioxidant response. Previous studies identified a nuclear localization signal (NLS) in the basic region and a nuclear exporting signal (NES) in the leucine zipper domain of Nrf2. In this study, we characterize a new functional NES (175LLSIPELQCLNI186) in the transactivation (TA) domain of Nrf2. A green fluorescence protein (GFP)-tagged Nrf2 segment (amino acids162-295) called GFP-NESTA exhibited a cytosolic distribution that could be disrupted by L184A mutation or leptomycin B treatment. Chimeric expression of this NESTA with a nuclear protein GAL4DBD could expel GAL4DBD into the cytoplasm. A variety of oxidants, including sulforaphane, tert-butylhydroquinone, and H2O2, could effectively induce nuclear translocation of GFP-NESTA. Mutational studies showed that cysteine 183 may mediate the redox response of NESTA. The discovery of multiple NLS/NES motifs in Nrf2 and the redox sensitivity of NESTA imply Nrf2 may be self-sufficient to sense and transduce oxidative signals into the nucleus, consequently initiating antioxidant gene transcription.

Original languageEnglish (US)
Pages (from-to)27251-27263
Number of pages13
JournalJournal of Biological Chemistry
Volume281
Issue number37
DOIs
StatePublished - Sep 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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