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细胞毒性天然产物威罗普利德 A 靶向核仁蛋白 14，核仁蛋白 14 对于核糖体生物发生是必需的。

The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis.

机构信息

Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München (TUM), Lichtenbergstrasse 4, 85747, Garching, Germany.

Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilian-University of Munich (LMU), Butenandtstrasse 5-13, 81377, Munich, Germany.

出版信息

Angew Chem Int Ed Engl. 2020 Jan 20;59(4):1595-1600. doi: 10.1002/anie.201911158. Epub 2019 Dec 12.

DOI:10.1002/anie.201911158
PMID:31658409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7004033/
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.

摘要

需要新的靶点来治疗癌症等毁灭性疾病。几十年来，天然产物通过针对多种途径为创新疗法提供了指导。受粘细菌 vioprolide A-D 的强大细胞毒性生物活性的启发，我们对其作用模式进行了深入研究。基于其对人急性淋巴细胞白血病 (ALL) 细胞的显著活性，我们进行了热蛋白质组谱 (TPP) 分析，并解析了 Jurkat 细胞中最活跃的衍生物 vioprolide A (VioA) 的靶蛋白。核仁蛋白 14 (NOP14) 在核糖体生物发生中是必不可少的，通过一系列蛋白质组学和生物学后续实验证实其为 VioA 的特异性靶标。与健康淋巴细胞相比，VioA 对 ALL 细胞的活性表明其通过一种新的作用模式具有独特的抗癌治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b853/7004033/501919c84720/ANIE-59-1595-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b853/7004033/501919c84720/ANIE-59-1595-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b853/7004033/f11d8ab9c008/ANIE-59-1595-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b853/7004033/7943b525972c/ANIE-59-1595-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b853/7004033/501919c84720/ANIE-59-1595-g005.jpg

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