This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hrdlicková, R.
Right arrow Articles by Bose, H. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hrdlicková, R.
Right arrow Articles by Bose, H. R., Jr.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2009, p. 929-941, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.00961-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Regulation of Telomerase Activity by Interferon Regulatory Factors 4 and 8 in Immune Cells{triangledown}

Radmila Hrdlicková, Jirí Nehyba, and Henry R. Bose Jr.*

Section of Molecular Genetics and Microbiology, School of Biological Sciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712-1095

Received 17 June 2008/ Returned for modification 21 July 2008/ Accepted 21 November 2008

Telomerase activity is downregulated in somatic cells but is upregulated during the activation of cells of the immune system. The mechanism of this reactivation is not well understood. In this study, we demonstrated that interferon regulatory factor 4 (IRF-4) and, to a lesser extent, IRF-8 induce telomerase activity. The suppression of IRF-4 results in decreased levels of TERT (telomerase reverse transcriptase) mRNA and telomerase activity and reduces cell proliferation. The overexpression of TERT compensates for this proliferation defect, suggesting that telomerase contributes to the regulation of cell proliferation by IRF-4. The induction of telomerase by IRF-4 and IRF-8 correlates with the activation of the TERT promoter. IRF-4 binds the interferon response-stimulated element and the gamma interferon-activated sequence composite binding site in the TERT core promoter region in vivo. Additionally, the binding of Sp1, Sp3, USF-1, USF-2, and c-Myc to the TERT promoter is elevated in cells expressing IRF-4. IRF-4, but not IRF-8, synergistically cooperates with Sp1 and Sp3 in the activation of the TERT promoter. Collectively, these results indicate that IRF-4 and IRF-8, two lymphoid cell-specific transcription factors, increase telomerase activity by activating TERT transcription in immune cells.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712-1095. Phone: (512) 471-5525. Fax: (512) 471-2130. E-mail: bose{at}mail.utexas.edu

{triangledown} Published ahead of print on 1 December 2008.

Molecular and Cellular Biology, February 2009, p. 929-941, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.00961-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»