Author/Authors :
Otto، نويسنده , , Tobias and Horn، نويسنده , , Sebastian and Brockmann، نويسنده , , Markus and Eilers، نويسنده , , Ursula and Schüttrumpf، نويسنده , , Lars and Popov، نويسنده , , Nikita and Kenney، نويسنده , , Anna Marie and Schulte، نويسنده , , Johannes H. and Beijersbergen، نويسنده , , Roderick and Christiansen، نويسنده , , Holger and Berwanger، نويسنده , , Bernd and Eilers، نويسنده , , Martin، نويسنده ,
Abstract :
Summary
an 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.
