title: Cell response of Escherichia coli to cisplatin-induced stress.
abstract: Cisplatin is undoubtedly one of the most common and successful anticancer drugs worldwide. Though its DNA-based mechanism of action is well established, the contribution of the proteome to this process remains unclear. The possible impact of particular Escherichia coli proteins on the cytostatic activity of cisplatin was the subject of this study. Our main focus was not only the "bottom-up" identification of novel cisplatin protein targets through LC/LC-MS/MS analysis, but also a label-free quantification of their regulation profile by spectral-counting. The regulation of two proteins, aconitate hydratase 2 and 60 kDa chaperonin 1, could be linked to a platinated amino acid in the protein sequence, whereas in the cases of 30S ribosomal protein S1 and enolase, it could be shown that cisplatin fragments are coordinated to an essential site for the functionality of the protein. Nucleoside triphosphate pyrophosphohydrolase (MazG) regulates the programmed cell death and was found to be platinated on the protein surface, which probably correlates with the established mode of action. A possible new chapter in the understanding of cisplatin's mechanism of action and its severe side effects is opened, since evidence is provided that platinated proteins are not only involved in cellular stress response but also in energy metabolism through glycolysis and catabolic processes, in gene regulatory mechanisms and protein synthesis.
authors.affiliation: Department of Analytical Chemistry, Ruhr University of Bochum, Bochum, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stefanopoulou
authors.forename: Malte
authors.initials: M
authors.lastname: Kokoschka
authors.forename: William S
authors.initials: WS
authors.lastname: Sheldrick
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Wolters
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011755:Pyrophosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D029968:Escherichia coli Proteins; C543726:MazG protein, E coli; D011755:Pyrophosphatases; D002945:Cisplatin