Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma

被引：472

作者：

Otto, Tobias ^{[5
]}

Horn, Sebastian ^{[5
]}

Brockmann, Markus ^{[5
]}

Eilers, Ursula ^{[5
]}

Schuettrumpf, Lars ^{[5
]}

Popov, Nikita ^{[5
]}

Kenney, Anna Marie ^{[1
]}

Schulte, Johannes H. ^{[2
]}

Beijersbergen, Roderick ^{[3
]}

Christiansen, Holger ^{[4
]}

Berwanger, Bernd ^{[4
]}

Eilers, Martin ^{[5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[2] Univ Hosp Essen, Dept Pediat Hematol Oncol & Endocrinol, D-45122 Essen, Germany

[3] Netherlands Canc Ctr, NL-1066 CX Amsterdam, Netherlands

[4] Univ Marburg, Childrens Hosp, Med Ctr, D-35043 Marburg, Germany

[5] Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany

来源：

CANCER CELL | 2009年 / 15卷 / 01期

关键词：

UBIQUITIN LIGASE; CENTROSOME AMPLIFICATION; DEPENDENT DEGRADATION; PROTEIN STABILITY; TUMOR-FORMATION; HUMAN-CELLS; KINASE-A; CYCLIN-E; C-MYC; PHOSPHORYLATION;

D O I：

10.1016/j.ccr.2008.12.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 ubiquitinates ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals.

引用

收藏

页码：67 / 78

页数：12

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