Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma.
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.
Mesh Terms:
Cell Cycle Proteins, Cell Line, Tumor, Cell Proliferation, F-Box Proteins, Humans, Neuroblastoma, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-myc, RNA Interference, Ubiquitin-Protein Ligases
Cell Cycle Proteins, Cell Line, Tumor, Cell Proliferation, F-Box Proteins, Humans, Neuroblastoma, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-myc, RNA Interference, Ubiquitin-Protein Ligases
Cancer Cell
Date: Jan. 06, 2009
PubMed ID: 19111882
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