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Papers In Press, published online ahead of print May 17, 2002
J. Biol. Chem, 10.1074/jbc.M203706200
Submitted on April 17, 2002
Revised on May 16, 2002
Accepted on May 17, 2002
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701
Corresponding Author: jchoe{at}mail.kaist.ac.kr
Transcriptional regulation of the hTERT gene is a critical step in transformation and differentiation. Human papillomavirus (HPV) E2 protein inhibits cell growth in HPV-infected cells and triggers apoptosis in HeLa cells. Since E2 induces cell growth suppression and senescence, we hypothesize that the protein may modulate cellular gene expression related to these processes. In this report, we demonstrate that E2 inhibits the human telomerase reverse transcriptase (hTERT) promoter. Mapping of the E2-reponsive region of hTERT reveals that Sp1 is important for E2-mediated repression of this promoter in 293T cells. Site-directed mutagenesis data on the hTERT promoter show that E2 does not abolish E-Box mediated transcription, and represses promoter activity via the Sp1 binding site. Furthermore, chromatin immunoprecipitation assays indicate that E2 is actively recruited to the hTERT promoter region. Our findings provide novel insights into the biological function of human papillomavirus E2.
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