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http://dx.doi.org/10.18419/opus-14589
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DC Element | Wert | Sprache |
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dc.contributor.author | Braun, Josef | - |
dc.contributor.author | Hu, Yudong | - |
dc.contributor.author | Jauch, Adrian T. | - |
dc.contributor.author | Gronauer, Thomas F. | - |
dc.contributor.author | Mergner, Julia | - |
dc.contributor.author | Bach, Nina C. | - |
dc.contributor.author | Traube, Franziska R. | - |
dc.contributor.author | Zahler, Stefan | - |
dc.contributor.author | Sieber, Stephan A. | - |
dc.date.accessioned | 2024-07-05T11:39:14Z | - |
dc.date.available | 2024-07-05T11:39:14Z | - |
dc.date.issued | 2024 | de |
dc.identifier.issn | 2691-3704 | - |
dc.identifier.other | 1894784324 | - |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-146086 | de |
dc.identifier.uri | http://elib.uni-stuttgart.de/handle/11682/14608 | - |
dc.identifier.uri | http://dx.doi.org/10.18419/opus-14589 | - |
dc.description.abstract | Neocarzilin (NCA) is a natural product exhibiting potent antimigratory as well as antiproliferative effects. While vesicle amine transport protein 1 (VAT-1) was previously shown to inhibit migration upon NCA binding, the molecular mechanisms responsible for impaired proliferation remained elusive. We here introduce a chemical probe closely resembling the structural and stereochemical features of NCA and unravel bone marrow stromal antigen 2 (BST-2) as one of the targets responsible for the antiproliferative effect of NCA in cancer cells. The antiproliferative mechanism of NCA was confirmed in corresponding BST-2 knockout (KO) HeLa cells, which were less sensitive to compound treatment. Vice versa, reconstitution of BST-2 in the KO cells again reduced proliferation upon NCA addition, comparable to that of wild-type (wt) HeLa cells. Whole proteome mass spectrometric (MS) analysis of NCA-treated wt and KO cancer cells revealed regulated pathways and showed reduced levels of BST-2 upon NCA treatment. In-depth analysis of BST-2 levels in response to proteasome and lysosome inhibitors unraveled a lysosomal degradation path upon NCA treatment. As BST-2 mediates the release of epidermal growth factor receptor (EGFR) from lipid rafts to turn on proliferation signaling pathways, reduced BST-2 levels led to attenuated phosphorylation of STAT3. Furthermore, fluorescence microscopy confirmed increased colocalization of EGFR and lipid rafts in the presence of NCA. Overall, NCA represents a versatile anticancer natural product with a unique dual mode of action and unconventional inhibition of proliferation via BST-2 degradation. | en |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft | de |
dc.description.sponsorship | China Scholarship Council | de |
dc.language.iso | en | de |
dc.relation.uri | doi:10.1021/jacsau.4c00039 | de |
dc.rights | info:eu-repo/semantics/openAccess | de |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | de |
dc.subject.ddc | 540 | de |
dc.subject.ddc | 570 | de |
dc.subject.ddc | 610 | de |
dc.title | Neocarzilin inhibits cancer cell proliferation via BST‑2 degradation, resulting in lipid raft-trapped EGFR | en |
dc.type | article | de |
dc.date.updated | 2024-06-19T17:25:01Z | - |
ubs.fakultaet | Chemie | de |
ubs.fakultaet | Fakultätsübergreifend / Sonstige Einrichtung | de |
ubs.institut | Institut für Biochemie und Technische Biochemie | de |
ubs.institut | Fakultätsübergreifend / Sonstige Einrichtung | de |
ubs.publikation.seiten | 1833-1840 | de |
ubs.publikation.source | JACS Au 4 (2024), S. 1833-1840 | de |
ubs.publikation.typ | Zeitschriftenartikel | de |
Enthalten in den Sammlungen: | 03 Fakultät Chemie |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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au4c00039.pdf | 4,32 MB | Adobe PDF | Öffnen/Anzeigen |
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