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Kirsch, V.C.* ; Orgler, C.* ; Braig, S.* ; Jeremias, I. ; Auerbach, D.* ; Müller, R.* ; Vollmar, A.M.* ; Sieber, S.A.*

The cytotoxic natural product vioprolide A targets nucleolar protein 14 essential for ribosome biogenesis.

Angew. Chem.-Int. Edit. 59, 1595-1600 (2019)
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Novel targets are needed for treatment of devastating diseases such as cancer. For decades, natural products have guided innovative therapies by addressing diverse pathways. Inspired by the potent cytotoxic bioactivity of myxobacterial vioprolides A-D, we performed in-depth studies on their mode of action. Based on its prominent potency against human acute lymphoblastic leukemia (ALL) cells, we conducted thermal proteome profiling (TPP) and deciphered the target proteins of the most active derivative vioprolide A (VioA) in Jurkat cells. Nucleolar protein 14 (NOP14), which is essential in ribosome biogenesis, was confirmed as a specific target of VioA by a suite of proteomic and biological follow-up experiments. Given its activity against ALL cells compared to healthy lymphocytes, VioA exhibits unique therapeutic potential for anticancer therapy through a novel mode of action.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acute Lymphoblastic Leukemia ; Natural Products ; Quantitative Proteomics ; Ribosomess ; Target Identification; Computational Platform; Identification; Emg1
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1433-7851
e-ISSN 1521-3773
Journal Angewandte Chemie - Internationale Edition
Quellenangaben Volume: 59, Issue: 4, Pages: 1595-1600 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Weinheim
Reviewing status Peer reviewed
Institute(s) Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Stem Cell and Neuroscience
PSP Element(s) G-506600-001
DOI 10.1002/anie.201911158
WOS ID WOS:000502151400001
Scopus ID 85076400631
PubMed ID 31658409
Erfassungsdatum 2019-12-23
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