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  • den Hollander, J, et al. (author)
  • Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
  • 2010
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:9, s. 1498-1505
  • Journal article (peer-reviewed)abstract
    • 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. (Blood. 2010;116(9):1498-1505)
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Type of publication
journal article (1)
Type of content
peer-reviewed (1)
Author/Editor
Keller, U (1)
Graf, N (1)
Nilsson, Jonas A. (1)
Buck, A (1)
Kremer, M (1)
Goga, A. (1)
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Peschel, C (1)
den Hollander, J (1)
Rimpi, Sara (1)
Doherty, JR (1)
Rudelius, M (1)
Hoellein, A (1)
Scheerer, M (1)
Hall, MA (1)
von Bubnoff, N (1)
Duyster, J (1)
Cleveland, JL (1)
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University
Umeå University (1)
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English (1)
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Medical and Health Sciences (1)
Year
2010 (1)

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