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通过结合调控DNA序列MARE （Maf识别元件）在执行氧化应激反应中发挥关键作用。Bach2是nrf2相关的转录抑制因子，是Maf癌蛋白家族的组织特异性伙伴。我们在这里展示了Bach2是如何被氧化应激敏感的条件核输出调节的。在培养细胞中，Bach2通过其c端进化保守的细胞质定位信号（CLS）定位于细胞质中。CLS诱导leptomycin b敏感核报告蛋白输出，提示其依赖核输出蛋白Crml/Exportinl。然而，CLS序列与富含亮氨酸的核输出信号并不相似，诱变分析表明，一段非疏水氨基酸是其活性所必需的。氧化应激源终止CLS活性，诱导Bach2核积累。众所周知，氧化应激可激活MARE依赖性转录，而在培养细胞中过度表达Bach2可抑制MARE的诱导性。结果表明，在哺乳动物细胞中，Bach2介导核胞质通讯，将氧化应激和转录抑制结合起来。

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.