| Project/Area Number |
11138205
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
IGARASHI Kazuhiko HIROSHIMA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR, 医学部, 教授 (00250738)
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| Project Period (FY) |
1999
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | transcription factor / Fos / Maf / oxidative stress / proliferation / cell death / nuclear export signal / Fos |
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| Research Abstract |
The mammalian transcription activator Nrf2 plays critical roles in executing oxidative stress response by binding to the regulatory DNA sequence MARE (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 Crml/Exportinl. However, the CLS sequence does not bear resemblance to the leucine-rich class of nuclear export signal, and mutagenesis analysis indicated that a stretch of non-hydrophobic amino acids are 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.
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