A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli*
A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli*
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DOI：
10.1074/jbc.m112.413070
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
M. Wenk;Qiaorui Ba;Veronika Erichsen;K. MacInnes;Heike Wiese;B. Warscheid;H. Koch
中科院分区：
文献类型：
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作者：
M. Wenk;Qiaorui Ba;Veronika Erichsen;K. MacInnes;Heike Wiese;B. Warscheid;H. Koch
背景：YchF是一种功能未知的普遍保守的ATP酶。结果：YchF抑制过氧化氢酶活性，高水平的YchF引起H2 O2超敏反应。YchF是负调节OxyR响应H2 O2。结论：YchF是一个普遍保守的氧化应激反应负调控因子，通过翻译后机制发挥作用。意义：这是YchF蛋白家族的第一个功能描述。YchF是一种功能未知的进化保守的ATP酶。在人类中，YchF同源物hOla 1似乎影响细胞增殖，并在许多肿瘤中被发现上调。也有人提出可能参与调节氧化应激反应，但缺乏有关潜在机制的详细信息。为了深入了解YchF的功能，我们使用大肠杆菌作为模式生物，发现YchF过表达导致H2 O2超敏反应。这不是由H2 O2清除酶的转录或翻译下调引起的。相反，我们观察到YchF依赖性抑制过氧化氢酶活性和直接相互作用的主要E。大肠杆菌过氧化氢酶KatG。KatG抑制依赖于YchF的ATP酶活性，并受翻译后修饰的调节，最有可能包括H2 O2依赖性去磷酸化。我们还表明，YchF的表达受到转录因子OxyR的抑制，并进一步在H2 O2的反应后进行修饰。总之，我们的数据表明，YchF功能作为一种新的负调节剂的氧化应激反应，在大肠杆菌。杆菌考虑到关于hOla 1的现有数据，YchF/Ola 1很可能在细菌和人类中执行类似的功能，并且它们的上调抑制了细胞抑制破坏活性氧的能力。
Background: YchF is a universally conserved ATPase of unknown function. Results: YchF inhibits catalase activity, and high YchF levels cause H2O2 hypersensitivity. YchF is negatively regulated by OxyR in response to H2O2. Conclusion: YchF is a universally conserved negative regulator of the oxidative stress response that acts by a post-translational mechanism. Significance: This is the first functional description of the YchF protein family. YchF is an evolutionarily conserved ATPase of unknown function. In humans, the YchF homologue hOla1 appears to influence cell proliferation and was found to be up-regulated in many tumors. A possible involvement in regulating the oxidative stress response was also suggested, but details on the underlying mechanism are lacking. For gaining insight into YchF function, we used Escherichia coli as a model organism and found that YchF overexpression resulted in H2O2 hypersensitivity. This was not caused by transcriptional or translational down-regulation of H2O2-scavenging enzymes. Instead, we observed YchF-dependent inhibition of catalase activity and a direct interaction with the major E. coli catalase KatG. KatG inhibition was dependent on the ATPase activity of YchF and was regulated by post-translational modifications, most likely including an H2O2-dependent dephosphorylation. We furthermore showed that YchF expression is repressed by the transcription factor OxyR and further post-translationally modified in response to H2O2. In summary, our data show that YchF functions as a novel negative regulator of the oxidative stress response in E. coli. Considering the available data on hOla1, YchF/Ola1 most likely execute similar functions in bacteria and humans, and their up-regulation inhibits the ability of the cells to scavenge damaging reactive oxygen species.