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The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis.
Kirsch, Volker C Orgler, Christina Braig, Simone Jeremias, Irmela Auerbach, David Müller, Rolf Vollmar, Angelika M Sieber, Stephan A
Kirsch, Volker C
Orgler, Christina
Braig, Simone
Jeremias, Irmela
Auerbach, David
Müller, Rolf
Vollmar, Angelika M
Sieber, Stephan A
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2020-01-20
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Abstract
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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Angew Chem Int Ed Engl. 2020 Jan 20;59(4):1595-1600. doi: 10.1002/anie.201911158. Epub 2019 Dec 12.
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en
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1521-3773
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Attribution-NonCommercial-ShareAlike 4.0 International