Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma Journal Article
| Authors: | Otto, T.; Horn, S.; Brockmann, M.; Eilers, U.; Schüttrumpf, L.; Popov, N.; Kenney, A. M.; Schulte, J. H.; Beijersbergen, R.; Christiansen, H.; Berwanger, B.; Eilers, M. |
| Article Title: | Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma |
| 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<sup>Fbxw7</sup> ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; human cell; protein function; cell proliferation; cell cycle proteins; cell cycle; reverse transcription polymerase chain reaction; apoptosis; gene amplification; gene expression; signaling; protein degradation; protein binding; rna interference; enzyme activity; cell line, tumor; neuroblastoma; neuroblastoma cell; protein-serine-threonine kinases; cellbio; proto-oncogene proteins c-myc; ubiquitin-protein ligases; protein c myb; humdisease; aurora a kinase; cyclin dependent kinase 1; nocodazole; f-box proteins |
| Journal Title: | Cancer Cell |
| Volume: | 15 |
| Issue: | 1 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2009-01-06 |
| Start Page: | 67 |
| End Page: | 78 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2008.12.005 |
| PUBMED: | 19111882 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 30 November 2010" - "CODEN: CCAEC" - "Source: Scopus" |
