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(Fbxw7) ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals.
authors.affiliation: Institute of Molecular Biology and Tumor Research, Marburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Otto
authors.forename: Sebastian
authors.initials: S
authors.lastname: Horn
authors.forename: Markus
authors.initials: M
authors.lastname: Brockmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Eilers
authors.forename: Lars
authors.initials: L
authors.lastname: Schüttrumpf
authors.forename: Nikita
authors.initials: N
authors.lastname: Popov
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Kenney
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Roderick
authors.initials: R
authors.lastname: Beijersbergen
authors.forename: Holger
authors.initials: H
authors.lastname: Christiansen
authors.forename: Bernd
authors.initials: B
authors.lastname: Berwanger
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
mesh_terms: D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D016271:Proto-Oncogene Proteins c-myc; D044767:Ubiquitin-Protein Ligases; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases