Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain
| Autor: | Siwang Yu, A.-N. Tony Kong, Wenge Li |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Transcriptional Activation
Leucine zipper NF-E2-Related Factor 2 Molecular Sequence Data Biology environment and public health Biochemistry Green fluorescent protein Transactivation NLS Animals Humans Amino Acid Sequence Nuclear protein Nuclear export signal Molecular Biology Transcription factor Cell Nucleus Nuclear Export Signals Cell Biology Hydrogen Peroxide respiratory system Cell biology Protein Structure Tertiary Fatty Acids Unsaturated Nuclear localization sequence HeLa Cells Subcellular Fractions |
| Zdroj: | The Journal of biological chemistry. 281(37) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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