REGULATION OF CELL PROLIFERATION BY CROSS-TALK OF BACH AND AP-1 TRANSCRIPTION FACTORS.

哺乳动物转录激活因子Nrf2通过与调控的DNA序列mARE(Maf识别元件)结合，在执行氧化应激反应中发挥关键作用。Bach2是一种与Nrf2相关的转录抑制因子，也是Maf癌蛋白家族的组织特异性伙伴。我们在这里展示了Bach2是如何受到氧化应激敏感的有条件核出口的调控。在培养细胞中，Bach2通过其进化保守的细胞质定位信号(CLS)定位于细胞质。CLS引导对瘦素B敏感的报告蛋白的核输出，表明它依赖于核输出蛋白Crm1/Exportin1。然而，CLS序列与富含亮氨酸的核输出信号并不相似，突变分析表明，一系列非疏水氨基酸是其活性所必需的。氧化应激源终止了CLS活性，诱导了Bach2的核积累。虽然已知氧化应激可以激活母马依赖的转录，但Bach2在培养细胞中的过表达抑制了MARE的诱导。结果表明，Bach2介导了哺乳动物细胞中氧化应激和转录抑制的核质通讯。

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.