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学科主题基础医学
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)
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
2014-03-01
DOI10.1016/j.bbamcr.2013.12.004
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
WOS记录号WOS:000330821000008
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
资助机构National Science Council of Taiwan ; National Cheng Kung University ; Kaohsiung Chang Gung Memorial Hospital
引用统计
被引频次:9[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/400002259/66359
专题北京大学基础医学院_病理学系
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
推荐引用方式
GB/T 7714
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.
APA Hsu, Che-Chia.,Chen, Chang-Han.,Hsu, Tsung-I.,Hung, Jan-Jong.,Ko, Jiunn-Liang.,...&Lin, Ding-Yen.(2014).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).BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1843(3),565-579.
MLA Hsu, Che-Chia,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)".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1843.3(2014):565-579.
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