The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein
文献类型：期刊论文
| 作者 | Zhao XD1,7; Heng JIT5; Guardavaccaro D6; Jiang R[1]1; Pagano M6; Guillemot F5; Iavarone A[*]1,2,3; Lasorella A[*]1,2,4 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2008 |
| 卷号 | 10期号:6页码:643-653 |
| 通讯作者 | al2179@columbia.edu ; ai2102@columbia.edu |
| 合作状况 | 其它 |
| 英文摘要 | Development of the nervous system requires that timely withdrawal from the cell cycle be coupled with initiation of differentiation. Ubiquitin-mediated degradation of the N-Myc oncoprotein in neural stem/progenitor cells is thought to trigger the arrest of proliferation and begin differentiation. Here we report that the HECT-domain ubiquitin ligase Huwe1 ubiquitinates the N-Myc oncoprotein through Lys 48-mediated linkages and targets it for destruction by the proteasome. This process is physiologically implemented by embryonic stem (ES) cells differentiating along the neuronal lineage and in the mouse brain during development. Genetic and RNA interference-mediated inactivation of the Huwe1 gene impedes N-Myc degradation, prevents exit from the cell cycle by opposing the expression of Cdk inhibitors and blocks differentiation through persistent inhibition of early and late markers of neuronal differentiation. Silencing of N-myc in cells lacking Huwe1 restores neural differentiation of ES cells and rescues cell-cycle exit and differentiation of the mouse cortex, demonstrating that Huwe1 restrains proliferation and enables neuronal differentiation by mediating the degradation of N-Myc. These findings indicate that Huwe1 links destruction of N-Myc to the quiescent state that complements differentiation in the neural tissue. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by grants from the NIH to A.L., A.I. and M.P. and an Emerald Foundation grant to D.G. D.G. is supported by a fellowship from Provincia di Benevento, Italy. J.H. is funded by the Australian NHMRC (ID:310616) and work in the F.G. laboratory is funded in part by an institutional grant from the Medical Research Council (UK). |
| 语种 | 英语 |
| 公开日期 | 2014-07-07 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7945]  |
| 专题 | 昆明动物研究所_科研共享资源 |
| 作者单位 | 1.Institute for Cancer Genetics,Columbia University Medical Center, New York, New York 10032, USA 2.Department of Pathology,Columbia University Medical Center, New York, New York 10032, USA 3.Department of Neurology,Columbia University Medical Center, New York, New York 10032, USA 4.Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA 5.Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK 6.Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue MSB 599, New York, New York 10016, USA 7.Shanghai Research Center for Model Organisms, Shanghai 201203, China |
| 推荐引用方式 GB/T 7714 | Zhao XD,Heng JIT,Guardavaccaro D,et al. The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein[J]. NATURE CELL BIOLOGY,2008,10(6):643-653. |
| APA | Zhao XD.,Heng JIT.,Guardavaccaro D.,Jiang R[1].,Pagano M.,...&Lasorella A[*].(2008).The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.NATURE CELL BIOLOGY,10(6),643-653. |
| MLA | Zhao XD,et al."The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein".NATURE CELL BIOLOGY 10.6(2008):643-653. |
入库方式： OAI收割
来源：昆明动物研究所
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