TY - JOUR
T1 - Telomerase activity does not always imply telomere maintenance
AU - Ouellette, Michel M.
AU - Aisner, Dara L.
AU - Savre-Train, Isabelle
AU - Wright, Woodring E.
AU - Shay, Jerry W.
N1 - Funding Information:
We thank Brian Frank, Jean-Franc¸ois Train for technical assistance, and Valerie M. Tesmer for insightful discussions. We wish to thank Geron Corporation (Menlo Park, CA) for the 1A4 monoclonal antibody against hTERT. This work was supported by the National Institute of Health (AG07992) (J.W.S. and W.E.W.) and Geron Corporation. J.W.S. is an Ellison Foundation Senior Scholar.
PY - 1999/1/27
Y1 - 1999/1/27
N2 - 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 assayed in 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.
AB - 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 assayed in 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.
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U2 - 10.1006/bbrc.1998.0114
DO - 10.1006/bbrc.1998.0114
M3 - Article
C2 - 9920820
AN - SCOPUS:0033608159
SN - 0006-291X
VL - 254
SP - 795
EP - 803
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -