title: A universally conserved ATPase regulates the oxidative stress response in Escherichia coli.
abstract: 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 H(2)O(2) hypersensitivity. This was not caused by transcriptional or translational down-regulation of H(2)O(2)-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 H(2)O(2)-dependent dephosphorylation. We furthermore showed that YchF expression is repressed by the transcription factor OxyR and further post-translationally modified in response to H(2)O(2). 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.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ), Stefan-Meier-Strasse 17, Freiburg, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Wenk
authors.forename: Qiaorui
authors.initials: Q
authors.lastname: Ba
authors.forename: Veronika
authors.initials: V
authors.lastname: Erichsen
authors.forename: Katherine
authors.initials: K
authors.lastname: MacInnes
authors.forename: Heike
authors.initials: H
authors.lastname: Wiese
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Koch
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D016877:Oxidants; D012097:Repressor Proteins; C499299:oxyR protein, E coli; D006861:Hydrogen Peroxide; D002374:Catalase; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C559743:YchF protein, E. coli; C522732:OLA1 protein, human