[PDF][PDF] Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma

T Otto, S Horn, M Brockmann, U Eilers, L Schüttrumpf… - Cancer cell, 2009 - cell.com
T Otto, S Horn, M Brockmann, U Eilers, L Schüttrumpf, N Popov, AM Kenney, JH Schulte…
Cancer cell, 2009cell.com
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 …
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 SCFFbxw7 ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals.
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