SseL Deubiquitinates RPS3 to Inhibit Its Nuclear Translocation.
SseL Deubiquitinates RPS3 to Inhibit Its Nuclear Translocation.
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DOI：
10.3390/pathogens7040086
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发表时间：
2018-11-07
期刊：
影响因子：
--
通讯作者：
Hardwidge PR
中科院分区：
文献类型：
--
作者：
Wu M;El Qaidi S;Hardwidge PR
许多革兰氏阴性细菌病原体使用III型分泌系统将毒力蛋白(效应物)输送到宿主细胞中，以抵消先天免疫。核糖体蛋白S3(RPS3)将核糖体蛋白κB亚基引导到特定的κB位点，在细菌感染的先天反应中发挥重要作用。两个大肠杆菌效应子抑制RPS3核转位。NleH1通过IKK-β抑制RPS3的磷酸化，这是RPS3核转位过程中的一个重要方面。P65的NleC蛋白降解产生一个N-末端的P65片段，竞争与RPS3结合的全长P65，从而也抑制RPS3的核转位。因此，大肠杆菌有多种机制来阻断RPS3介导的转录激活。考虑到这一点，我们考虑了其他肠道病原体是否也编码影响这一重要宿主调控途径的T3SS效应器。在这里，我们报道了沙门氏菌分泌效应因子L(SSEL)，它以前被证明是一种去泛素酶并抑制NF-κB信号，也通过去泛素化这一重要的宿主转录辅助因子来抑制RPS3核转位。SSEL对RPS3的脱泛素化仅限于K63-键，突变SSEL活性部位的半胱氨酸使其丧失脱泛素能力，从而抑制RPS3核转位。因此，沙门氏菌还编码至少一个T3SS效应器，改变宿主核中的RPS3活动。
Many Gram-negative bacterial pathogens use type III secretion systems to deliver virulence proteins (effectors) into host cells to counteract innate immunity. The ribosomal protein S3 (RPS3) guides NF-κB subunits to specific κB sites and plays an important role in the innate response to bacterial infection. Two E. coli effectors inhibit RPS3 nuclear translocation. NleH1 inhibits RPS3 phosphorylation by IKK-β, an essential aspect of the RPS3 nuclear translocation process. NleC proteolysis of p65 generates an N-terminal p65 fragment that competes for full-length p65 binding to RPS3, thus also inhibiting RPS3 nuclear translocation. Thus, E. coli has multiple mechanisms by which to block RPS3-mediated transcriptional activation. With this in mind, we considered whether other enteric pathogens also encode T3SS effectors that impact this important host regulatory pathway. Here we report that the Salmonella Secreted Effector L (SseL), which was previously shown to function as a deubiquitinase and inhibit NF-κB signaling, also inhibits RPS3 nuclear translocation by deubiquitinating this important host transcriptional co-factor. RPS3 deubiquitination by SseL was restricted to K63-linkages and mutating the active-site cysteine of SseL abolished its ability to deubiquitinate and subsequently inhibit RPS3 nuclear translocation. Thus, Salmonella also encodes at least one T3SS effector that alters RPS3 activities in the host nucleus.
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影响因子：
14.5
作者：
Gregory, RC;Taniguchi, T;D'Andrea, AD
通讯作者：
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影响因子：
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DOI：
10.1016/j.bbamcr.2008.10.017
发表时间：
2009-02-01
影响因子：
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16
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16
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通讯作者：
Bennett, Eric J.