Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
2010 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 116, no 9, 1498-1505 p.Article in journal (Refereed) Published
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)
Place, publisher, year, edition, pages
2010. Vol. 116, no 9, 1498-1505 p.
c-myc, transcriptional control, dna-replication, growth arrest, target genes, in-vivo, apoptosis, suppression, progression, inhibitor
IdentifiersURN: urn:nbn:se:umu:diva-43181DOI: 10.1182/blood-2009-11-251074ISI: 000281572700017OAI: oai:DiVA.org:umu-43181DiVA: diva2:412352