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The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis
Author(s) -
Kirsch Volker C.,
Orgler Christina,
Braig Simone,
Jeremias Irmela,
Auerbach David,
Müller Rolf,
Vollmar Angelika M.,
Sieber Stephan A.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201911158
Subject(s) - ribosome biogenesis , jurkat cells , cytotoxic t cell , ribosome inactivating protein , mode of action , biology , natural product , proteome , biogenesis , computational biology , ribosome , microbiology and biotechnology , chemistry , rna , cancer research , bioinformatics , immunology , biochemistry , in vitro , gene , t cell , immune system
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.