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Differential regulation of telomerase activity by six telomerase subunits.
Eur J Biochem. 2002 Jul; 269(14):3442-50.EJ

Abstract

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. Through down- or upregulation of telomerase, we found that only hTERT expression changed proportionally with the level of telomerase activity. The other components, TEP1, hTR, 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 hTERT subunit, which showed differential expression in normal and cancer tissues, all other components were expressed in both normal and malignant tissues. We conclude that hTERT is a regulatable subunit, whereas the other components are expressed more constantly in cells. Although hTERT has a rate-limiting effect on enzyme activity, the other telomerase subunits (hTR, TEP1, hsp90, p23, dyskerin) participated in full enzyme activity. We hypothesize that once hTERT is expressed, all other telomerase subunits can be assembled to form a highly active holoenzyme.

Authors+Show Affiliations

Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12135483

Citation

Chang, Joseph Tung-Chieh, et al. "Differential Regulation of Telomerase Activity By Six Telomerase Subunits." European Journal of Biochemistry, vol. 269, no. 14, 2002, pp. 3442-50.
Chang JT, Chen YL, Yang HT, et al. Differential regulation of telomerase activity by six telomerase subunits. Eur J Biochem. 2002;269(14):3442-50.
Chang, J. T., Chen, Y. L., Yang, H. T., Chen, C. Y., & Cheng, A. J. (2002). Differential regulation of telomerase activity by six telomerase subunits. European Journal of Biochemistry, 269(14), 3442-50.
Chang JT, et al. Differential Regulation of Telomerase Activity By Six Telomerase Subunits. Eur J Biochem. 2002;269(14):3442-50. PubMed PMID: 12135483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of telomerase activity by six telomerase subunits. AU - Chang,Joseph Tung-Chieh, AU - Chen,Yin-Ling, AU - Yang,Huei-Ting, AU - Chen,Chi-Yuan, AU - Cheng,Ann-Joy, PY - 2002/7/24/pubmed PY - 2002/9/18/medline PY - 2002/7/24/entrez SP - 3442 EP - 50 JF - European journal of biochemistry JO - Eur J Biochem VL - 269 IS - 14 N2 - 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. Through down- or upregulation of telomerase, we found that only hTERT expression changed proportionally with the level of telomerase activity. The other components, TEP1, hTR, 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 hTERT subunit, which showed differential expression in normal and cancer tissues, all other components were expressed in both normal and malignant tissues. We conclude that hTERT is a regulatable subunit, whereas the other components are expressed more constantly in cells. Although hTERT has a rate-limiting effect on enzyme activity, the other telomerase subunits (hTR, TEP1, hsp90, p23, dyskerin) participated in full enzyme activity. We hypothesize that once hTERT is expressed, all other telomerase subunits can be assembled to form a highly active holoenzyme. SN - 0014-2956 UR - https://www.unboundmedicine.com/medline/citation/12135483/Differential_regulation_of_telomerase_activity_by_six_telomerase_subunits_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=2002&volume=269&issue=14&spage=3442 DB - PRIME DP - Unbound Medicine ER -