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学科主题: 基础医学
题名:
The 58-kDa microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF)
作者: Hsu, Che-Chia1; Chen, Chang-Han8; Hsu, Tsung-I1,3; Hung, Jan-Jong1,2,3,4; Ko, Jiunn-Liang9; Zhang, Bo10; Lee, Yi-Chao6,7; Chen, Han-Ku11; Chang, Wen-Chang2,3,5,6; Lin, Ding-Yen1,2,3,4
关键词: 58-kDa microspherule protein ; Telomerase ; Human telomerase reverse transcriptase ; Telomerase transcriptional element-interacting factor
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
发表日期: 2014-03-01
DOI: 10.1016/j.bbamcr.2013.12.004
卷: 1843, 期:3, 页:565-579
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: CATALYTIC SUBUNIT HTERT ; HUMAN TUMOR-CELLS ; CANCER-CELLS ; C-MYC ; CHROMOSOME INSTABILITY ; DOWN-REGULATION ; IMMORTAL CELLS ; UP-REGULATION ; DNA-DAMAGE ; ACTIVATION
英文摘要:

58-kDa microspherule protein (MSP58) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. Currently, the mechanisms underlying the oncogenic effect of MSP58 are not fully understood. The human telomerase reverse transcriptase (hTERT) gene, which encodes an essential component for telomerase activity that is involved in cellular immortalization and transformation, is strictly regulated at the gene transcription level. Our previous study revealed a novel function of MSP58 in cellular senescence. Here we identify telomerase transcriptional element-interacting factor (TEIF) as a novel MSP58-interacting protein and determine the effect of MSP58 on hTERT transcription. This study thus provides evidence showing MSP58 to be a negative regulator of hTERT expression and telomerase activity. Luciferase reporter assays indicated that MSP58 could suppress the transcription of hTERT promoter. Additionally, stable overexpression of MSP58 protein in HT1080 and 293T cells decreased both endogenous hTERT expression and telomerase activity. Conversely, their upregulation was induced by MSP58 silencing. Chromatin immunoprecipitation assays showed that MSP58 binds to the hTERT proximal promoter. Furthermore, overexpression of MSP58 inhibited TEIF-mediated hTERT transactivation, telomerase activation, and cell proliferation promotion. The inhibitory effect of MSP58 occurred through inhibition of TEIF binding to DNA. Ultimately, the HT1080-implanted xenograft mouse model confirmed these cellular effects. Together, our findings provide new insights into both the biological function of MSP58 and the regulation of telomerase/hTERT expression. (C) 2013 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: NSC98-2320-B-006-035-MY3 ; NSC101-2320-B-038-022 ; NSC 100-2320-B-182A-001 (NMRPG8A0011) ; C015 ; CMRPG8A0391 ; CMRPG8A0392 ; CMRPG890921 ; CMRPG8B1251
项目资助者: National Science Council of Taiwan ; National Cheng Kung University ; Kaohsiung Chang Gung Memorial Hospital
WOS记录号: WOS:000330821000008
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66359
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Natl Cheng Kung Univ, Coll Biosci & Biotechnol, Inst Bioinfomat & Biosignal Transduct, Tainan 70101, Taiwan
2.Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan
3.Natl Cheng Kung Univ, Infect Dis & Signaling Res Ctr, Tainan 70101, Taiwan
4.Taipei Med Univ, Coll Med, Inst Canc Biol & Drug Discovery, Taipei 11031, Taiwan
5.Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei 11031, Taiwan
6.Taipei Med Univ, Ctr Neurotrauma & Neuroregenerat, Taipei 11031, Taiwan
7.Taipei Med Univ, Coll Med Sci & Technol, Program Neural Regenerat Med, Taipei 11031, Taiwan
8.Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung 83301, Taiwan
9.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 10091, Peoples R China
10.Chung Shan Med Univ, Inst Med, Taichung 40201, Taiwan
11.Yuans Gen Hosp, Dept Pathol, Kaohsiung 80249, Taiwan

Recommended Citation:
Hsu, Che-Chia,Chen, Chang-Han,Hsu, Tsung-I,et al. The 58-kDa microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF)[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2014,1843(3):565-579.
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