TY - JOUR
T1 - Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain
AU - Li, Wenge
AU - Yu, Si Wang
AU - Kong, A. N.Tony
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33748752586&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748752586&partnerID=8YFLogxK
U2 - 10.1074/jbc.M602746200
DO - 10.1074/jbc.M602746200
M3 - Article
C2 - 16790425
AN - SCOPUS:33748752586
SN - 0021-9258
VL - 281
SP - 27251
EP - 27263
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -