Telomerase Activity Does Not Always Imply Telomere Maintenance
The forced expression of the catalytic subunit of human telomerase, hTERT, produces telomerase activity, allows telomere maintenance, and extends the cellular life span of IMR90 human lung fibroblasts. The mutation D869A abolishes both the catalytic activity of hTERT and its ability to extend cellul...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1999-01, Vol.254 (3), p.795-803 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Ouellette, Michel M. Aisner, Dara L. Savre-Train, Isabelle Wright, Woodring E. Shay, Jerry W. |
| description | The forced expression of the catalytic subunit of human telomerase, hTERT, produces telomerase activity, allows telomere maintenance, and extends the cellular life span of IMR90 human lung fibroblasts. The mutation D869A abolishes both the catalytic activity of hTERT and its ability to extend cellular life span, demonstrating that the immortalizing capabilities of the enzyme are dependent on active catalysis. A second mutant of hTERT was examined that contains three copies of an HA epitope inserted at the C-terminus. This mutant produced telomerase activity in fibroblasts that was virtually indistinguishable from that of wild type telomerase when assayedin vitro.However, the forced expression of this mutant failed to maintain telomeres or extend cellular life span. Our results show that the catalytic activity of hTERT is required for cellular immortalization but that the presence of active telomerase does not necessarily imply telomere maintenance and immortality. |
| doi_str_mv | 10.1006/bbrc.1998.0114 |
| format | Article |
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The mutation D869A abolishes both the catalytic activity of hTERT and its ability to extend cellular life span, demonstrating that the immortalizing capabilities of the enzyme are dependent on active catalysis. A second mutant of hTERT was examined that contains three copies of an HA epitope inserted at the C-terminus. This mutant produced telomerase activity in fibroblasts that was virtually indistinguishable from that of wild type telomerase when assayedin vitro.However, the forced expression of this mutant failed to maintain telomeres or extend cellular life span. 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The mutation D869A abolishes both the catalytic activity of hTERT and its ability to extend cellular life span, demonstrating that the immortalizing capabilities of the enzyme are dependent on active catalysis. A second mutant of hTERT was examined that contains three copies of an HA epitope inserted at the C-terminus. This mutant produced telomerase activity in fibroblasts that was virtually indistinguishable from that of wild type telomerase when assayedin vitro.However, the forced expression of this mutant failed to maintain telomeres or extend cellular life span. 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| subjects | Base Sequence Catalytic Domain Cell Line DNA Primers Genetic Vectors Humans Lung - cytology Lung - metabolism Molecular Sequence Data Retroviridae - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Telomerase - genetics Telomerase - metabolism Telomere - enzymology |
| title | Telomerase Activity Does Not Always Imply Telomere Maintenance |
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