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学科主题: 基础医学
题名:
Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers
作者: Gong, Y.; Sun, Y.; McNutt, M. A.; Sun, Q.; Hou, L.; Liu, H.; Shen, Q.; Ling, Y.; Chi, Y.; Zhang, B.
关键词: centrosome ; DNA damage ; telomere dysfunction ; cancer
刊名: ONCOGENE
发表日期: 2009-03-01
DOI: 10.1038/onc.2008.503
卷: 28, 期:12, 页:1549-1560
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: CHROMOSOMAL INSTABILITY ; GENETIC INSTABILITY ; TUMOR-VIRUSES ; I TAX ; CELLS ; PROTEINS ; 11Q13 ; MICROTUBULE ; BREAKPOINTS ; CHECKPOINT
英文摘要:

Centrosome amplification and telomere shortening, which are commonly detected in human cancers, have been implicated in the induction of chromosome instability in tumorigenesis. The functions of these two structures are closely related to DNA damage repair machinery, and some factors that operate in the maintenance of telomeres also take part in the regulation of centrosome status, suggesting they are functionally linked. We report that TEIF (telomerase transcriptional elements-interacting factor), a transactivator of the hTERT (human telomerase reverse transcriptase subunit) gene, is distributed in the centrosome throughout the cell cycle, but its transport into the centrosome is increased under some conditions, and its distribution is dependent on its C-terminal domain. Experimental modulation of TEIF expression through overexpression, polypeptide expression or depletion affected centrosome status and increased abnormalities of cell mitosis. Localization of TEIF to the centrosome was also stimulated by treatment with genotoxic agents and experimental telomere dysfunction, accompanying centrosome amplification. Moreover, we demonstrated that the expression level of TEIF is not only closely correlated with centrosome amplification in soft tissue sarcomas but it is also significantly related to tumor histologic grade. Our data confirmed TEIF functions as a centrosome regulator. Its participation in DNA damage response, including telomere dysfunction and tumorigenesis, indicates TEIF is likely to be a factor involved in linking centrosome amplification and telomere dysfunction in cancer development.

语种: 英语
所属项目编号: 30570691 ; 20040001147
项目资助者: National Natural Science Foundation of China ; Doctors Program Foundations of Ministry Education
WOS记录号: WOS:000264537400007
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50573
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Gong, Y.,Sun, Y.,McNutt, M. A.,et al. Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers[J]. ONCOGENE,2009,28(12):1549-1560.
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