Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (151K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (47)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Crowe, D. L.
Right arrow Articles by Kyo, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crowe, D. L.
Right arrow Articles by Kyo, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2001, Vol. 29, No. 13 2789-2794
© 2001 Oxford University Press

E2F-1 represses transcription of the human telomerase reverse transcriptase gene

David L. Crowe*, Dan C. Nguyen, Kenneth J. Tsang and Satoru Kyo1 Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA and 1Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa 920-0934, Japan

The ends of human chromosomes (telomeres) lose up to 200 bp of DNA per cell division. Chromosomal shortening ultimately leads to senescence and death in normal cells. Many human carcinoma lines are immortal in vitro, suggesting that these cells have a mechanism for maintaining the ends of their chromosomes. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA onto chromosomes using its RNA component as template. Telomerase activity is found in most tumor cells, but is absent from normal cells. Little is known about how normal human cells repress telomerase (hTERT) gene expression. Mice carrying an E2F-1 null mutation develop a variety of malignant tumors, suggesting that this transcription factor has a tumor suppressor function. To determine mechanisms by which E2F-1 suppresses tumor formation, we examined the role of this transcription factor in regulation of the hTERT promoter in human cells. We identified two putative E2F-1-binding sites proximal to the transcriptional start site of the hTERT promoter. Mutation of these sites produced dramatic increases in promoter activity. Overexpression of E2F-1 but not a mutant E2F-1 repressed hTERT promoter activity in reporter gene assays. This repression was abolished by mutation of the E2F-1-binding sites in the hTERT promoter. Human cancer cell lines stably overexpressing E2F-1 exhibited decreased hTERT mRNA expression and telomerase activity. We conclude that E2F-1 has an atypical function as a transcriptional repressor of the hTERT gene in human cells.

* To whom correspondence should be addressed. Tel: +1 323 442 3170; Fax: +1 323 442 2981; Email: dcrowe{at}hsc.usc.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
M. Tozluoglu, E. Karaca, T. Haliloglu, and R. Nussinov
Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis
Nucleic Acids Res., September 1, 2008; 36(15): 5033 - 5049.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. N. Chau, L. H. El Touny, S. Jagadeesh, and P. P. Banerjee
Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3
Carcinogenesis, November 1, 2007; 28(11): 2282 - 2290.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Liu, X. Fang, Z. Ge, M. Jalink, S. Kyo, M. Bjorkholm, A. Gruber, J. Sjoberg, and D. Xu
The Telomerase Reverse Transcriptase (hTERT) Gene Is a Direct Target of the Histone Methyltransferase SMYD3
Cancer Res., March 15, 2007; 67(6): 2626 - 2631.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
S. Wang, C. Hu, and J. Zhu
Transcriptional Silencing of a Novel hTERT Reporter Locus during In Vitro Differentiation of Mouse Embryonic Stem Cells
Mol. Biol. Cell, February 1, 2007; 18(2): 669 - 677.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. N. Davis, K. J. Wojno, S. Daignault, M. D. Hofer, R. Kuefer, M. A. Rubin, and M. L. Day
Elevated E2F1 Inhibits Transcription of the Androgen Receptor in Metastatic Hormone-Resistant Prostate Cancer
Cancer Res., December 15, 2006; 66(24): 11897 - 11906.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Jagadeesh, S. Kyo, and P. P. Banerjee
Genistein Represses Telomerase Activity via Both Transcriptional and Posttranslational Mechanisms in Human Prostate Cancer Cells
Cancer Res., February 15, 2006; 66(4): 2107 - 2115.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. M. Alonso, J. Fueyo, J. W. Shay, K. D. Aldape, H. Jiang, O.-H. Lee, D. G. Johnson, J. Xu, Y. Kondo, T. Kanzawa, et al.
Expression of Transcription Factor E2F1 and Telomerase in Glioblastomas: Mechanistic Linkage and Prognostic Significance
J Natl Cancer Inst, November 2, 2005; 97(21): 1589 - 1600.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Quante, S. Heeg, A. von Werder, G. Goessel, C. Fulda, M. Doebele, H. Nakagawa, R. Beijersbergen, H. E. Blum, and O. G. Opitz
Differential transcriptional regulation of human telomerase in a cellular model representing important genetic alterations in esophageal squamous carcinogenesis
Carcinogenesis, November 1, 2005; 26(11): 1879 - 1889.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Wang and J. Zhu
The hTERT Gene Is Embedded in a Nuclease-resistant Chromatin Domain
J. Biol. Chem., December 31, 2004; 279(53): 55401 - 55410.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Borras, J. M. Esteve, J. R. Vina, J. Sastre, J. Vina, and F. V. Pallardo
Glutathione Regulates Telomerase Activity in 3T3 Fibroblasts
J. Biol. Chem., August 13, 2004; 279(33): 34332 - 34335.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Won, S. Chang, S. Oh, and T. K. Kim
Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells
PNAS, August 3, 2004; 101(31): 11328 - 11333.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
I. Horikawa and J. C. Barrett
Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms
Carcinogenesis, July 1, 2003; 24(7): 1167 - 1176.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Wang and J. Zhu
Evidence for a Relief of Repression Mechanism for Activation of the Human Telomerase Reverse Transcriptase Promoter
J. Biol. Chem., May 23, 2003; 278(21): 18842 - 18850.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Szutorisz, J. Lingner, A. P. Cuthbert, D. A. Trott, R. F. Newbold, and M. Nabholz
A Chromosome 3-encoded Repressor of the Human Telomerase Reverse Transcriptase (hTERT) Gene Controls the State of hTERT Chromatin
Cancer Res., February 1, 2003; 63(3): 689 - 695.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. J. Mauro and D. N. Foster
Regulators of Telomerase Activity
Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 521 - 524.
[Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.