Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma

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• 作者：Tobias Otto ; Sebastian Horn ; Markus Brockmann ; Ursula Eilers ; Lars Schü ; ttrumpf ; Nikita Popov ; Anna Marie Kenney ; Johannes H. Schulte ; Roderick Beijersbergen ; Holger Christiansen ; Bernd Berwanger ; Martin Eilers
• 刊名：Cancer Cell
• 出版年：2009
• 出版时间：6 January 2009
• 年：2009
• 卷：15
• 期：1
• 页码：67-78
• 全文大小：1691 K

文摘

Summary

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.