Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element.
The mammalian transcription activator Nrf2 plays critical roles in executing oxidative stress response by binding to the regulatory DNA sequence Maf recognition element. Bach2 is an Nrf2-related transcription repressor and a tissue-specific partner of the Maf oncoprotein family. We show here how Bach2 is regulated by an oxidative stress-sensitive conditional nuclear export. In cultured cells, Bach2 was localized in cytoplasm through its C-terminal evolutionarily conserved cytoplasmic localization signal (CLS). The CLS directed leptomycin B-sensitive nuclear export of reporter proteins, suggesting its dependence on the nuclear exporter Crm1/exportin 1. However, the CLS sequence does not bear a resemblance to the leucine-rich class of nuclear export signal, and mutagenesis analysis indicated that a stretch of nonhydrophobic amino acids is essential for its activity. Oxidative stressors aborted the CLS activity and induced nuclear accumulation of Bach2. Whereas oxidative stress is known to activate MARE-dependent transcription, overexpression of Bach2 in cultured cells silenced the inducibility of MARE. The results suggest that Bach2 mediates nucleocytoplasmic communication to couple oxidative stress and transcription repression in mammalian cells.
Hoshino
H
H
Department of Biochemistry, Tohoku University School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.
Kobayashi
A
A
Yoshida
M
M
Kudo
N
N
Oyake
T
T
Motohashi
H
H
Hayashi
N
N
Yamamoto
M
M
Igarashi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D017124:Conserved Sequence; D003545:Cysteine; D003593:Cytoplasm / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C491123:BACH2 protein, human; C486316:Bach1 protein, mouse; C102109:Bach2 protein, mouse; D001426:Bacterial Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D005231:Fatty Acids, Unsaturated; C081169:Maf protein, Bacillus subtilis; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D003545:Cysteine; C038753:leptomycin B