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Hu, Y.* ; Mostert, D.* ; Orgler, C.* ; Andler, O.* ; Zischka, H. ; Kazmaier, U.* ; Vollmar, A.* ; Braig, S.* ; Sieber, S.* ; Zahler, S.*

Thermal proteome profiling reveals insight to antiproliferative and pro-apoptotic effects of Lagunamide A in the modulation of DNA damage repair.

ChemBioChem:e202400024 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Affinity Based Protein Profiling ; Dna Damage ; Lagunamide A ; Tpp ; Thermal Protein Profiling; Cancer; Dephosphorylation; Identification; Survival; Binding; Eya3
ISSN (print) / ISBN 1439-4227
e-ISSN 1439-7633
Journal ChemBioChem
Quellenangaben Volume: , Issue: , Pages: , Article Number: e202400024 Supplement: ,
Publisher Wiley
Publishing Place Postfach 101161, 69451 Weinheim, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)
Grants Merck Future Insight Prize
Chinese Scholarship Council (CSC)