Degradation of the HilC and HilD regulator proteins by ATP-dependent Lon protease leads to downregulation of Salmonella pathogenicity island 1 gene expression
Degradation of the HilC and HilD regulator proteins by ATP-dependent Lon protease leads to downregulation of Salmonella pathogenicity island 1 gene expression
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DOI：
10.1111/j.1365-2958.2004.04425.x
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发表时间：
2005-02-01
影响因子：
3.6
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Takaya, A;Kubota, Y;Yamamoto, T
沙门氏菌致病岛1（SPI 1）使感染沙门氏菌能够穿过小肠屏障，并通过诱导细胞凋亡来逃避吞噬。几种环境信号和转录调节因子调节hilA的表达，hilA编码的蛋白质在SPI 1基因表达的调控层次中起着核心作用。我们以前已经表明，Lon，应激诱导的ATP依赖性蛋白酶，是一个负调节hilA，这表明它的目标是激活hilA表达所需的因素。为了阐明Lon蛋白酶负调控SPI 1转录的机制，我们寻找其底物蛋白。我们发现，HilC和HilD，这是hilA表达的正调控，在Lon-depleted细胞中积累，并且在Lon-disrupted突变体中发生的SPI 1表达的增强在Lon-hilC hilD三重无效突变体中没有观察到。此外，我们证明了HilC和HilD的半衰期在Lon-depleted突变体中分别比在Lon（+）细胞中长约12倍和3倍，表明Lon靶向HilC和HilD两者。鉴于这些研究结果，我们认为，SPI 1的表达调控是负控制通过降解的HilC和HilD转录调节Lon。
Salmonella pathogenicity island 1 (SPI1) enables infecting Salmonella to cross the small intestinal barrier and to escape phagocytosis by inducing apoptosis. Several environmental signals and transcriptional regulators modulate the expression of hilA, which encodes a protein playing a central role in the regulatory hierarchy of SPI1 gene expression. We have previously shown that Lon, a stress-induced ATP-dependent protease, is a negative regulator of hilA, suggesting that it targets factors required for activating hilA expression. To elucidate the mechanisms by which Lon protease negatively regulates SPI1 transcription, we looked for its substrate proteins. We found that HilC and HilD, which are positive regulators of hilA expression, accumulate in Lon-depleted cells, and that the enhancement of SPI1 expression that occurs in a lon-disrupted mutant is not observed in the lon hilC hilD triple null mutant. Furthermore, we demonstrated that the half-lives of HilC and HilD are, respectively, about 12 times and three times longer in the Lon-depleted mutant, than in the Lon(+) cells, suggesting that Lon targets both of HilC and HilD. In view of these findings, we suggest that the regulation of SPI1 expression is negatively controlled through degradation of the HilC and HilD transcriptional regulators by Lon.