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Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts

H Hoshino1, A Kobayashi, M Yoshida

  • 1Department of Biochemistry, Tohoku University School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.

The Journal of Biological Chemistry
|May 16, 2000
PubMed

Insights

Bach2, a transcription repressor, is exported from the nucleus via a novel signal sensitive to oxidative stress. This mechanism links oxidative stress to transcription repression in mammalian cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key activator of the oxidative stress response.
  • Bach2 is a repressor related to Nrf2 and partners with the Maf oncoprotein family.
  • Oxidative stress response involves regulating transcription factors that bind to Maf recognition elements (MARE).

Purpose of the Study:

  • To investigate the regulation of Bach2 by oxidative stress.
  • To identify the mechanism of Bach2's nucleocytoplasmic transport.
  • To determine Bach2's role in MARE-dependent transcription under oxidative stress.

Main Methods:

  • Utilized cultured cells to study Bach2 localization and function.
  • Employed reporter proteins and mutagenesis to analyze the cytoplasmic localization signal (CLS) of Bach2.
  • Assessed the effect of oxidative stressors on Bach2 nuclear export and MARE inducibility.

Main Results:

  • Bach2 is localized in the cytoplasm via a C-terminal CLS, dependent on Crm1/exportin 1.
  • The Bach2 CLS is a novel non-leucine-rich nuclear export signal.
  • Oxidative stress inhibits Bach2 export, causing nuclear accumulation and repression of MARE inducibility.

Conclusions:

  • Bach2 is regulated by an oxidative stress-sensitive nuclear export mechanism.
  • Bach2 acts as a mediator of nucleocytoplasmic communication linking oxidative stress to transcription repression.
  • The findings reveal a novel pathway for controlling gene expression during oxidative stress.

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