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- W2113396317 abstract "ABSTRACT Telomerase maintains cell viability and chromosomal stability through the addition of telomere repeats to chromosome ends. The reactivation of telomerase through the upregulation of TERT, the telomerase protein subunit, is an important step during cancer development, yet TERT protein function and regulation remain incompletely understood. Despite its close sequence similarity to human TERT (hTERT), we find that mouse TERT (mTERT) does not immortalize primary human fibroblasts. Here we exploit these differences in activity to understand TERT protein function by creating chimeric mouse-human TERT proteins. Through the analysis of these chimeric TERT proteins, we find that sequences in the human carboxy-terminal domain are critical for telomere maintenance in human fibroblasts. The substitution of the human carboxy-terminal sequences into the mouse TERT protein is sufficient to confer immortalization and maintenance of telomere length and function. Strikingly, we find that hTERT protein accumulates to markedly higher levels than does mTERT protein and that the sequences governing this difference in protein regulation also reside in the carboxy-terminal domain. These elevated protein levels, which are characteristic of hTERT, are necessary but not sufficient for telomere maintenance because stabilized mTERT mutants cannot immortalize human cells. Thus, the TERT carboxy terminus contains sequences that regulate TERT protein levels and determinants that are required for productive action on telomere ends." @default.
- W2113396317 created "2016-06-24" @default.
- W2113396317 creator A5017267551 @default.
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- W2113396317 creator A5066185271 @default.
- W2113396317 creator A5075929117 @default.
- W2113396317 date "2006-03-15" @default.
- W2113396317 modified "2023-09-26" @default.
- W2113396317 title "Regulation of Cellular Immortalization and Steady-State Levels of the Telomerase Reverse Transcriptase through Its Carboxy-Terminal Domain" @default.
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- W2113396317 doi "https://doi.org/10.1128/mcb.26.6.2146-2159.2006" @default.
- W2113396317 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1430280" @default.
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