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Titel: Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency
VerfasserIn: Martínez-Limón, Adrían
Calloni, Giulia
Ernst, Robert
Vabulas, R. Martin
Sprache: Englisch
Titel: Cell Death & Disease
Bandnummer: 11
Heft: 9
Verlag/Plattform: Springer Nature
Erscheinungsjahr: 2020
Freie Schlagwörter: Enzymes
Lipidomics
Protein folding
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Tumor cells adapt their metabolism to meet the energetic and anabolic requirements of high proliferation and invasiveness. The metabolic addiction has motivated the development of therapies directed at individual biochemical nodes. However, currently there are few possibilities to target multiple enzymes in tumors simultaneously. Flavincontaining enzymes, ca. 100 proteins in humans, execute key biotransformations in mammalian cells. To expose metabolic addiction, we inactivated a substantial fraction of the flavoproteome in melanoma cells by restricting the supply of the FMN and FAD precursor riboflavin, the vitamin B2. Vitamin B2 deficiency affected stability of many polypeptides and thus resembled the chaperone HSP90 inhibition, the paradigmatic multiple-target approach. In support of this analogy, flavin-depleted proteins increasingly associated with a number of proteostasis network components, as identified by the mass spectrometry analysis of the FAD-free NQO1 aggregates. Proteome-wide analysis of the riboflavin-starved cells revealed a profound inactivation of the mevalonate pathway of cholesterol synthesis, which underlines the manifold cellular vulnerability created by the flavoproteome inactivation. Cell cyclearrested tumor cells became highly sensitive to alkylating chemotherapy. Our data suggest that the flavoproteome is well suited to design synthetic lethality protocols combining proteostasis manipulation and metabolic reprogramming.
DOI der Erstveröffentlichung: 10.1038/s41419-020-02929-5
URL der Erstveröffentlichung: https://doi.org/10.1038/s41419-020-02929-5
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-422334
hdl:20.500.11880/37918
http://dx.doi.org/10.22028/D291-42233
ISSN: 2041-4889
Datum des Eintrags: 21-Jun-2024
Bezeichnung des in Beziehung stehenden Objekts: Supplementary information
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1038%2Fs41419-020-02929-5/MediaObjects/41419_2020_2929_MOESM1_ESM.docx
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Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Medizinische Biochemie und Molekularbiologie
Professur: M - Prof. Dr. Robert Ernst
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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