Integration of fluxome and transcriptome data in Saccharomyces cerevisiae offers unique features of doxorubicin and imatinib

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dc.contributor.authorTaymaz-Nikerel, Hilal
dc.date.accessioned2024-07-18T20:56:58Z
dc.date.available2024-07-18T20:56:58Z
dc.date.issued2021
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractImproving the efficacy of drugs and developing new drugs are required to compensate for drug resistance. Therefore, it is critical to unveil the mode of action, which can be studied through the cellular response at genome-scale, of the existing drugs. Here, system-level response of Saccharomyces cerevisiae, a eukaryotic model microorganism, to two chemotherapy drugs doxorubicin and imatinib used against cancer are analysed. While doxorubicin is mainly known to interact with DNA through intercalation and imatinib is known to inhibit the activity of the tyrosine kinase enzyme, the exact mechanisms of action for both drugs have not been determined. The response of S. cerevisiae cells to long-term stress by these drugs under controlled aerobic conditions was investigated and analyzed by the genome-wide transcriptome and genome-wide fluxes. The classification of adverse and similar responses of a certain gene at a transcriptional versus flux level indicated the possible regulatory mechanisms under these different stress conditions. Most of the biochemical reactions were found to be regulated at a post-transcriptional or metabolic level, whereas fewer were regulated at a transcriptional level for both stress cases. Furthermore, disparately induced and repressed pathways in the metabolic network under doxorubicin and imatinib stress were identified. The glycolytic and pentose phosphate pathways responded similarly, whereas the purine-histidine metabolic pathways responded differently. Then, a comparison of differential fluxes and differentially co-expressed genes under doxorubicin and imatinib stress provided the potential common and unique features of these drugs. Analyzing such regulatory differences helps in resolving drug mechanisms and suggesting new drug targets.en_US
dc.identifier.doi10.1039/d1mo00003a
dc.identifier.endpage789en_US
dc.identifier.issn2515-4184
dc.identifier.issue5en_US
dc.identifier.pmid34279019en_US
dc.identifier.scopus2-s2.0-85117400376en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage783en_US
dc.identifier.urihttps://doi.org/10.1039/d1mo00003a
dc.identifier.urihttps://hdl.handle.net/11411/8930
dc.identifier.volume17en_US
dc.identifier.wosWOS:000674359700001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherRoyal Soc Chemistryen_US
dc.relation.ispartofMolecular Omicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTyrosine Kinase Inhibitorsen_US
dc.subjectProteomic Analysisen_US
dc.subjectProteinen_US
dc.subjectCanceren_US
dc.subjectCellsen_US
dc.subjectExpressionen_US
dc.subjectStressen_US
dc.subjectDamageen_US
dc.titleIntegration of fluxome and transcriptome data in Saccharomyces cerevisiae offers unique features of doxorubicin and imatinib
dc.typeArticle

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