onr:"swepub:oai:DiVA.org:umu-43181"
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- den Hollander, J (author)
Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
- Article/chapterEnglish2010
Publisher, publication year, extent ...
- American Society of Hematology,2010
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:umu-43181
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-43181URI
- https://doi.org/10.1182/blood-2009-11-251074DOI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- 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)
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Hematologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Hematology hsv//eng
- c-myc
- transcriptional control
- dna-replication
- growth arrest
- target genes
- in-vivo
- apoptosis
- suppression
- progression
- inhibitor
Added entries (persons, corporate bodies, meetings, titles ...)
- Rimpi, SaraUmeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)(Swepub:umu)saarii98 (author)
- Doherty, JR (author)
- Rudelius, M (author)
- Buck, A (author)
- Hoellein, A (author)
- Kremer, M (author)
- Graf, N (author)
- Scheerer, M (author)
- Hall, MA (author)
- Goga, A (author)
- von Bubnoff, N (author)
- Duyster, J (author)
- Peschel, C (author)
- Cleveland, JL (author)
- Nilsson, Jonas AUmeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)(Swepub:umu)josnin95 (author)
- Keller, U (author)
- Umeå universitetInstitutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet) (creator_code:org_t)
Related titles
- In:Blood: American Society of Hematology116:9, s. 1498-15050006-49711528-0020
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- den Hollander, J
- Rimpi, Sara
- Doherty, JR
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- Kremer, M
- Graf, N
- Scheerer, M
- Hall, MA
- Goga, A
- von Bubnoff, N
- Duyster, J
- Peschel, C
- Cleveland, JL
- Nilsson, Jonas A
- Keller, U
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