2005年9月
Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells
MOLECULAR AND CELLULAR BIOLOGY
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- 巻
- 25
- 号
- 18
- 開始ページ
- 8037
- 終了ページ
- 8043
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1128/MCB.25.18.8037-8043.2005
- 出版者・発行元
- AMER SOC MICROBIOLOGY
The transcriptional regulation of the human telomerase catalytic subunit (hTERT) plays a critical role in telomerase activity. Approximately 200 by of the proximal core promoter is responsible for basic hTERT expression; however, the function of the distal regulatory elements remains unclear. The transcription factor activator protein 1 (AP-1) is involved in cellular proliferation, differentiation, carcinogenesis, and apoptosis and is expressed broadly in both cancer and normal cells. There are several putative AP-1 sites in the hTERT promoter, but their functions are unknown. The present study examined the regulatory role of AP-1 in hTERT gene transcription. Overexpression of AP-1 leads to transcriptional suppression of hTERT in cancer cells. The combination of c-Fos and c-Jun or c-Fos and JunD strongly suppresses hTERT promoter activity in transient-expression analyses. The hTERT promoter region between -2000 and -378 is responsible for this function. Gel shift and supershift analyses, as well as ChIP, show binding of JunD and c-Jun on two putative AP-1 sites within this region. Mutations in the AP-1 binding sites rescued suppressions caused by AP-1, suggesting this is a direct regulation of the hTERT promoter. In contrast, there was no effect on mTERT expression or mTERT promoter activity by AP-1 overexpression in mouse fibroblasts. The species-specific function of AP-1 in TERT expression may in part help explain the difference in telomerase activity between normal human and mouse cells.
- リンク情報
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- DOI
- https://doi.org/10.1128/MCB.25.18.8037-8043.2005
- CiNii Articles
- http://ci.nii.ac.jp/naid/10024009458
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/16135795
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000231651200010&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1128/MCB.25.18.8037-8043.2005
- ISSN : 0270-7306
- CiNii Articles ID : 10024009458
- PubMed ID : 16135795
- Web of Science ID : WOS:000231651200010