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den Hollander, Jürgen; Rimpi, Sara; Doherty, Joanne R.; Rudelius, Martina; Buck, Andreas; Hoellein, Alexander; Kremer, Marcus; Graf, Nikolas; Scheerer, Markus; Hall, Mark A.; Goga, Andrei; von Bubnoff, Nikolas; Duyster, Justus; Peschel, Christian; Cleveland, John L.; Nilsson, Jonas A.; Keller, Ulrich

Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state

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  • Media type: E-Article
  • Title: Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
  • Contributor: den Hollander, Jürgen; Rimpi, Sara; Doherty, Joanne R.; Rudelius, Martina; Buck, Andreas; Hoellein, Alexander; Kremer, Marcus; Graf, Nikolas; Scheerer, Markus; Hall, Mark A.; Goga, Andrei; von Bubnoff, Nikolas; Duyster, Justus; Peschel, Christian; Cleveland, John L.; Nilsson, Jonas A.; Keller, Ulrich
  • imprint: American Society of Hematology, 2010
  • Published in: Blood
  • Language: English
  • DOI: 10.1182/blood-2009-11-251074
  • ISSN: 0006-4971; 1528-0020
  • Origination:
  • Footnote:
  • Description: <jats:p>Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function.</jats:p>
  • Access State: Open Access