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

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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis ; volume:59 ; number:4 ; year:2020 ; pages:1595-1600 ; extent:6
Angewandte Chemie / International edition. International edition ; 59, Heft 4 (2020), 1595-1600 (gesamt 6)

Urheber
Kirsch, Volker C.
Orgler, Christina
Braig, Simone
Jeremias, Irmela
Auerbach, David
Müller, Rolf
Vollmar, Angelika M.
Sieber, Stephan A.

DOI
10.1002/anie.201911158
URN
urn:nbn:de:101:1-2022061313271592524896
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:22 MESZ

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Beteiligte

  • Kirsch, Volker C.
  • Orgler, Christina
  • Braig, Simone
  • Jeremias, Irmela
  • Auerbach, David
  • Müller, Rolf
  • Vollmar, Angelika M.
  • Sieber, Stephan A.

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