Cell response of Escherichia coli to cisplatin-induced stress

• Published in: Proteomics (Weinheim) Vol. 11; no. 21; pp. 4174 - 4188
• Main Authors: Stefanopoulou, Maria, Kokoschka, Malte, Sheldrick, William S., Wolters, Dirk A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.11.2011; WILEY‐VCH Verlag; Wiley-VCH; Wiley Subscription Services, Inc
• Subjects: Aconitate hydratase; Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Apoptosis; Biological and medical sciences; Chaperonins; Cisplatin; Cisplatin - pharmacology; Cytostatic cell response; E coli; Energy metabolism; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial - drug effects; Glycolysis; Medical research; Microbiology; Miscellaneous; Mode of action; Models, Molecular; Molecular Sequence Data; nucleoside triphosphates; Nucleoside-triphosphate pyrophosphatase; Phosphopyruvate hydratase; Protein biosynthesis; Protein synthesis; Proteins; proteomics; Pyrophosphatases - chemistry; Pyrophosphatases - genetics; Pyrophosphatases - metabolism; ribosomal protein S1; Side effects; Stress; Microbiology; Escherichia coli; Proteomics; Bacteria; Cisplatin; Stress; Cytostatic cell response; Enterobacteriaceae
• ISSN: 1615-9853; 1615-9861; 1615-9861
• DOI: 10.1002/pmic.201100203

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.