Opposing regulatory roles of E2F in human telomerase reverse transcriptase (hTERT) gene expression in human tumor and normal somatic cells1
JAEJOON WON*, JEONGBIN YIM* and TAE KOOK KIM,2
* National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea; and Institute of Chemistry and Cell Biology, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
2 Correspondence: Depar tment of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea.
Human cells with high proliferative potential, such as tumor cells or stem cells, exhibit telomerase activity whereas most normal human somatic cells do not. Telomerase activity is tightly regulated by the expression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). Through an expression cloning approach, we identified E2F-1 as a repressor of the hTERT gene in human tumor cells. Detailed analyses of E2Fs indicated that: E2F-1, E2F-2, and E2F-3 (but not E2F-4 and E2F-5) repressed hTERT promoter through Sp sites in human tumor cells, whereas all five E2Fs activated hTERT promoter through E2F sites in normal human somatic cells. These contrasting effects of E2F transcription factors on the hTERT promoter may contribute to the paradoxical biological activities of E2F, which can both promote and inhibit cellular proliferation and tumorigenesis.