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Cancer Cell. 2009 Jan 6;15(1):67-78. doi: 10.1016/j.ccr.2008.12.005.

Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma.

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1
Institute of Molecular Biology and Tumor Research, Marburg, Germany.

Abstract

In human neuroblastoma, amplification of the MYCN gene predicts poor prognosis and resistance to therapy. In a shRNA screen of genes that are highly expressed in MYCN-amplified tumors, we have identified AURKA as a gene that is required for the growth of MYCN-amplified neuroblastoma cells but largely dispensable for cells lacking amplified MYCN. Aurora A has a critical function in regulating turnover of the N-Myc protein. Degradation of N-Myc requires sequential phosphorylation by cyclin B/Cdk1 and Gsk3. N-Myc is therefore degraded during mitosis in response to low levels of PI3-kinase activity. Aurora A interacts with both N-Myc and the SCF(Fbxw7) ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals.

PMID:
19111882
DOI:
10.1016/j.ccr.2008.12.005
[Indexed for MEDLINE]
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