tailieunhanh - Báo cáo Y học: Differential regulation of telomerase activity by six telomerase subunits

Telomerase is a specialized reverse transcriptase responsible for synthesizing telomeric DNA at the ends of chromosomes. Six subunits composing the telomerase complex have been cloned: hTR (human telomerase RNA), TEP1 (telomerase-associated protein 1), hTERT (human telomerase reverse transcriptase), hsp90 (heat shock protein 90), p23, and dyskerin. In this study, we investigated the role of each the telomerase subunit on the activity of telomerase. | Eur. J. Biochem. 269 3442-3450 2002 FEBS 2002 doi Differential regulation of telomerase activity by six telomerase subunits Joseph Tung-Chieh Chang1 Yin-Ling Chen2 Huei-Ting Yang2 Chi-Yuan Chen2 and Ann-Joy Cheng2 1 Department of Radiation Oncology Chang Gung Memorial Hospital Taoyuan Taiwan 2School of Medical Technology and Graduate School of Basic Medical Science Chang Gung University Taoyuan Taiwan Telomerase is a specialized reverse transcriptase responsible for synthesizing telomeric DNA at the ends of chromosomes. Six subunits composing the telomerase complex have been cloned hTR Ịlmman lelomesase NAA EEPI telomerase-associated protein 1 hTETT human telomerase reverse transcriptase hsp90 heat shock protein 90 p23 and dyskerin. In this study we investigated the role of each the telomerase subunit on the activity of telomerase. Through down- or upregulation of telomerase we found that only hTETT expression changed proportionally with the level of telomerase activity. The other components TEE1 hTT hsp90 p23 and dyskerin remained at high and unchanged levels throughout modulation. In vivo and in vitro experiments with antisense oligonucleotides against each telomerase component were also performed. Telomerase activity was decreased or abolished by antisense treatment. To correlate clinical sample status four pairs of normal and malignant tissues from patients with oral cancer were examined. Except for the hTETT subunit which showed differential expression in normal and cancer tissues all other components were expressed in both normal and malignant tissues. We conclude that hTETT is a regulatable subunit whereas the other components are expressed more constantly in cells. Although hTETT has a rate-limiting effect on enzyme activity the other telomerase subunits hTT TEE1 hsp90 p23 dyskerin participated in full enzyme activi ty. We hypothesize that once hTETT is expressed all other telomerase subunits can be assembled to form a .

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