Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1
Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1
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DOI：
10.1038/sj.emboj.7600248
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发表时间：
2004-07-07
期刊：
影响因子：
11.4
通讯作者：
Igarashi, K
中科院分区：
文献类型：
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作者：
Suzuki, H;Tashiro, S;Igarashi, K
Bach1 是血红素加氧酶 1 和 β-珠蛋白基因的转录抑制因子，已知这两个基因均由血红素诱导转录。为了检验血红素调节 Bach1 活性的假设，我们在人 293T 和 GM02063 细胞中表达 Bach1 的野生型和突变版本，连同或不连同其异二聚体伴侣 MafK，并检查它们的亚细胞定位。血红素合成的抑制增强了 Bach1 的核积累，而用血红素处理细胞则导致 Bach1 的核排除。虽然 Bach1 的镉诱导核输出信号 (NES) 对于血红素反应是可有可无的，但发现包含两个血红素结合基序的区域对于血红素诱导的核排除至关重要。该区域作为血红素调节的 NES 发挥作用，依赖于输出者 Crm1。这些结果扩展了血红素在蛋白质分选中的调节作用，并表明 Bach1 将代谢活动转化为基因表达。
Bach1 is a transcriptional repressor of heme oxygenase-1 and beta-globin genes, both of which are known to be transcriptionally induced by heme. To test the hypothesis that heme regulates the activity of Bach1, we expressed wild type and mutated versions of Bach1 together with or without its heterodimer partner MafK in human 293T and GM02063 cells and examined their subcellular localization. Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. While the cadmium-inducible nuclear export signal (NES) of Bach1 was dispensable for the heme response, a region containing two of the heme-binding motifs was found to be critical for the heme-induced nuclear exclusion. This region functioned as a heme-regulated NES dependent on the exporter Crm1. These results extend the regulatory roles for heme in protein sorting, and suggest that Bach1 transduces metabolic activity into gene expression.