期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 4, 页码 1595-1600出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201911158
关键词
acute lymphoblastic leukemia; natural products; quantitative proteomics; ribosomess; target identification
资金
- Deutsche Forschungsgemeinschaft [FOR1409]
- Center for Integrated Protein Science
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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