This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takakura, M. Articles by Shay, J. W. Search for Related Content PubMed PubMed Citation Articles by Takakura, M. Articles by Shay, J. W.

Function of AP-1 in Transcription of the Telomerase Reverse Transcriptase Gene (TERT) in Human and Mouse Cells

Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039,¹ Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa, Ishikawa 920-8641, Japan²

Received 12 April 2005/ Returned for modification 3 May 2005/ Accepted 5 July 2005

The transcriptional regulation of the human telomerase catalytic subunit (hTERT) plays a critical role in telomerase activity. Approximately 200 bp 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.

This article has been cited by other articles:

• Bellon, M., Nicot, C. (2008). Regulation of Telomerase and Telomeres: Human Tumor Viruses Take Control. JNCI J Natl Cancer Inst 100: 98-108 [Abstract] [Full Text]  
• DWYER, J., LI, H., XU, D., LIU, J.-P. (2007). Transcriptional Regulation of Telomerase Activity: Roles of the the Ets Transcription Factor Family. Ann. N. Y. Acad. Sci. 1114: 36-47 [Abstract] [Full Text]  
• LI, H., LIU, J.-P. (2007). Mechanisms of Action of TGF-beta in Cancer: Evidence for Smad3 as a Repressor of the hTERT Gene. Ann. N. Y. Acad. Sci. 1114: 56-68 [Abstract] [Full Text]  
• Wooten-Blanks, L. G., Song, P., Senkal, C. E., Ogretmen, B. (2007). Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1. FASEB J. 21: 3386-3397 [Abstract] [Full Text]  
• Katzenellenbogen, R. A., Egelkrout, E. M., Vliet-Gregg, P., Gewin, L. C., Gafken, P. R., Galloway, D. A. (2007). NFX1-123 and Poly(A) Binding Proteins Synergistically Augment Activation of Telomerase in Human Papillomavirus Type 16 E6-Expressing Cells. J. Virol. 81: 3786-3796 [Abstract] [Full Text]  
• Li, H., Xu, D., Li, J., Berndt, M. C., Liu, J.-P. (2006). Transforming Growth Factor beta Suppresses Human Telomerase Reverse Transcriptase (hTERT) by Smad3 Interactions with c-Myc and the hTERT Gene. J. Biol. Chem. 281: 25588-25600 [Abstract] [Full Text]