IR@PKUHSC  > 北京大学基础医学院  > 病原生物学系
学科主题基础医学
Impaired nuclear export of tumor-derived c-terminal truncated cyclin D1 mutant in ESCC cancer
Hao, Meili3; Chen, Xiangmei1,2; Zhang, Ting1,2; Shen, Tao1,2; Xie, Qing1,2; Xing, Xiujuan1,2; Gui, Hongxi3; Lu, Fengmin1,2
关键词cyclin D1 cyclin-dependent kinase 4 nuclear export cell proliferation cancer
刊名ONCOLOGY LETTERS
2011-11-01
DOI10.3892/ol.2011.404
2期:6页:1203-1211
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者National Natural Science Foundation of China ; National S and T Major Project for Infectious Diseases ; National Natural Science Foundation of China ; National S and T Major Project for Infectious Diseases
研究领域[WOS]Oncology
关键词[WOS]SQUAMOUS-CELL CARCINOMA ; PROTEASOMAL DEGRADATION ; RETINOBLASTOMA PROTEIN ; BREAST-CANCER ; DNA-DAMAGE ; PHOSPHORYLATION ; GENE ; EXPRESSION ; OVEREXPRESSION ; PROTEOLYSIS
英文摘要

Cyclin D1 is a significant regulator of the G1- to S-phase transition and is often aberrant in human tumors of various origins. Although cancer-derived cyclin D1 mutants are potent oncogenes in vitro and in vivo, the mechanisms by which they contribute to neoplasia remaind to be elucidated. We previously identified a cyclin D1 mutation (Delta 266-295) in esophageal cancer with deleted codons from 266 to 295 of wild-type cyclin D1, the critical COOH-terminal regulatory sequences necessary for cyclin D1 nuclear export. In the present study, this cancer-derived cyclin D1-Delta 266-295 was shown to be a constitutively nuclear cyclin D1 protein with a significantly increased oncogenic potential. Moreover, the cancer-derived cyclin D1-Delta 266-295 mutant was found to retain its ability to bind to and activate CDK4, which in turn phosphorylates and inactivates the pRb protein and promotes cell cycle progression. In comparison to wild-type cyclin D1a, D1-Delta 266-295 exhibited enforced nuclear accumulation. In addition, the transient transfection and ectopic expression of this nuclear localized D1-Delta 266-295 up-regulated endogenous Notchl expression, indicating that the mutant retained its ability as a transcriptional regulator. Furthermore, data from the flow cytometry assay showed that D1-Delta 266-295 fractionally increased >4N cell accumulation, and further analysis suggested the retriggering of DNA replication relevant to its inhibition of Cdt1 proteolysis. Therefore, the inappropriate nuclear localization of this cyclin D1 mutant may interfere with DNA replication in cultured cells, thereby contributing to genomic instability.

语种英语
所属项目编号30771099 ; 2009ZX10004-903
资助者National Natural Science Foundation of China ; National S and T Major Project for Infectious Diseases ; National Natural Science Foundation of China ; National S and T Major Project for Infectious Diseases
WOS记录号WOS:000295390800030
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52124
Collection北京大学基础医学院_病原生物学系
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Beijing 100191, Peoples R China
3.Harbin Med Coll, Dept Microbiol, Harbin 150081, Heilongjiang, Peoples R China
Recommended Citation
GB/T 7714
Hao, Meili,Chen, Xiangmei,Zhang, Ting,et al. Impaired nuclear export of tumor-derived c-terminal truncated cyclin D1 mutant in ESCC cancer[J]. ONCOLOGY LETTERS,2011,2(6):1203-1211.
APA Hao, Meili.,Chen, Xiangmei.,Zhang, Ting.,Shen, Tao.,Xie, Qing.,...&Lu, Fengmin.(2011).Impaired nuclear export of tumor-derived c-terminal truncated cyclin D1 mutant in ESCC cancer.ONCOLOGY LETTERS,2(6),1203-1211.
MLA Hao, Meili,et al."Impaired nuclear export of tumor-derived c-terminal truncated cyclin D1 mutant in ESCC cancer".ONCOLOGY LETTERS 2.6(2011):1203-1211.
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