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学科主题: 基础医学
题名:
Mutations in Fbx4 inhibit dimerization of the SCFFbx4 ligase and contribute to cyclin D1 overexpression in human cancer
作者: Barbash, Olena1,2; Zamfirova, Petia1; Lin, Douglas I.1,2; Chen, Xiangmei5; Yang, Ke5; Nakagawa, Hiroshi3,4; Lu, Fengmin5; Rustgi, Anil K.3,4; Diehl, J. Alan1,2
刊名: CANCER CELL
发表日期: 2008-07-01
DOI: 10.1016/j.ccr.2008.05.017
卷: 14, 期:1, 页:68-78
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: PHOSPHORYLATION-DEPENDENT UBIQUITINATION ; F-BOX PROTEINS ; BREAST-CANCER ; NUCLEAR EXPORT ; PROTEOLYSIS ; DEGRADATION ; EXPRESSION ; COMPLEX ; KINASE ; ONCOGENE
英文摘要:

SCFFbx4 was recently identified as the E3 ligase for cyclin D1. We now describe cell-cycle-dependent phosphorylation and dimerization of Fbx4 that is regulated by GSK3 beta and is defective in human cancer. We present data demonstrating that a pathway involving Ras-Akt-GSK3 beta controls the temporal phosphorylation and dimerization of the SCFFbx4 E3 ligase. Inhibition of Fbx4 activity results in accumulation of nuclear cyclin D1 and oncogenic transformation. The importance of this regulatory pathway for normal cell growth is emphasized by the prevalence of mutations in Fbx4 in human cancer that impair dimerization. Collectively, these data reveal that inactivation of the cyclin D1 E3 ligase likely contributes to cyclin D1 overexpression in a significant fraction of human cancer.

语种: 英语
WOS记录号: WOS:000257655100010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52804
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
2.Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
3.Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA
4.Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA
5.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100083, Peoples R China

Recommended Citation:
Barbash, Olena,Zamfirova, Petia,Lin, Douglas I.,et al. Mutations in Fbx4 inhibit dimerization of the SCFFbx4 ligase and contribute to cyclin D1 overexpression in human cancer[J]. CANCER CELL,2008,14(1):68-78.
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