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Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers
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
2009-03-01
DOI10.1038/onc.2008.503
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
资助者National Natural Science Foundation of China ; Doctors Program Foundations of Ministry Education ; National Natural Science Foundation of China ; Doctors Program Foundations of Ministry Education
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
资助者National Natural Science Foundation of China ; Doctors Program Foundations of Ministry Education ; National Natural Science Foundation of China ; Doctors Program Foundations of Ministry Education
WOS记录号WOS:000264537400007
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50573
专题基础医学院_病理学系
作者单位Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100191, Peoples R China
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GB/T 7714
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.
APA Gong, Y..,Sun, Y..,McNutt, M. A..,Sun, Q..,Hou, L..,...&Zhang, B..(2009).Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers.ONCOGENE,28(12),1549-1560.
MLA Gong, Y.,et al."Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers".ONCOGENE 28.12(2009):1549-1560.
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