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The cytotoxic natural product vioprolide A targets nucleolar protein 14 essential for ribosome biogenesis.
Angew. Chem.-Int. Edit. 59, 1595-1600 (2019)
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
ISSN (print) / ISBN
1433-7851
e-ISSN
1521-3773
Quellenangaben
Volume: 59,
Issue: 4,
Pages: 1595-1600
Publisher
Wiley
Publishing Place
Weinheim
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)