KMID : 0978920020030040049
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Korean Journal of Clinical Geriatrics 2002 Volume.3 No. 4 p.49 ~ p.58
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Transcriptional regulation of human telomerase catalytic subunit(hTERT) by Ras and ElA
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Kim Tae-Kyung
Park Si-Bog Lee Kyu-Hoon Kim Yong-Seok
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Abstract
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Telomere length is maintained by the telomerase which is a ribonucleoprotein polymerase. In normal human cells, telomere length is not maintained and telomerase is not active except sperm and stem cells. However, in tumors, telomerase becomes active. Telomere length is a molecular clock determining cellular fate toward apoptosis, senescence or immortalization. So telomerase, as a key factor for telomere length has been studied to figure out its control mechanism. Human telomerase catalytic subunit(hTERT), as a component of teloemrase was identified as a determining factor of telomerase activity. So this study was focused on the role of ras and E1A as the possible factors involved in transcriptional control of hTERT. Ras activated hTERT promoter activity for more than two folds in MCF7 and SaOS2 cells but inhibited hTERT promoter activity in HepG2 and ZR75 cells. So the transcriptional effect of ras on hTERT promoter must be determined by cellular contexts, like accessory factors and other transcriptional factors. E1A activated hTERT promoter activity up to ten folds in HepG2 and SaOS2 cells. So E1A, as a transcriptional activator of hTERT promoter, is considered to have synergic relationships with other factors from cellular contexts because E1A strongly activated hTERT promoter activity in hTERT positive HepG2 cells in comparison with the degree of activation for hTERT in hTERT negative SaOS2 cells. Finally, it is possible that Ras and E1A are the key factors in hTERT transcription. However, further study is necessary to decide the binding factor(s) which must be interacting with Ras or E1A to access their response element on hTERT promoter.
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KEYWORD
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Telomere, Telemorase, Human telomerase catalytic subunit(hTERl), Ras, E1A
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