The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter
Abstract
Telomerase, the enzyme that synthesizes telomeric DNA, is not expressed in most human somatic cells but is activated with in vitro immortalization and during tumorigenesis, and repressed by cell differentiation. Of the two components of the core enzyme, the catalytic protein hTERT is limiting for activity. To investigate mechanisms of hTERT gene regulation, we have cloned genomic sequences encompassing the complete hTERT transcription unit. The hTERT gene consists of 16 exons and 15 introns spanning approximately 35 kb. Transient transfections of immortal human cells with potential regulatory 5' sequences linked to a reporter, combined with deletion analysis of these sequences, indicated that elements responsible for promoter activity are contained within a region extending from 330 bp upstream of the ATG to the second exon of the gene. Assays in different cell types have shown that the hTERT promoter is inactive in normal and in transformed pre-immortal cells, but, like telomerase, it is activated with cell immortalization. Sequence analysis revealed that the hTERT promoter is GC-rich, lacks TATA and CAAT boxes but contains binding sites for several transcription factors that may be involved in its regulation. The abundance of these sites suggests the possibility that hTERT expression may be subject to multiple levels of control and be regulated by different factors in different cellular contexts.
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Cites
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Characteristics of a human cell line transformed by DNA from human adenovirus type 5
Graham, F. L., Russell, W. C., Smiley, J., & Nairn, R. (1977) · Journal of General Virology · doi:10.1099/0022-1317-36-1-59 · Cited by 4,793
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
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“HA1 cells are HEK cells transformed by SV40 T-antigen; they do not express telomerase activity or hTERT prior to crisis but express both on immortalization (13).”
BackgroundMeyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784
Shizuya, H., Birren, B., Kim, U. J., Mancino, V, Slepak, T., Tachiiri, Y., & Simon, M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.18.8794 · Cited by 1,671
Vaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003 · cited 2×
“The res ulting shortening of the telomeres limits the cell proliferative lifespan, as recently demonstrated by the finding that restoration of telomerase activity to somatic cells leads to bypass of cell senescence (11,12).”
BackgroundWeinrich, S. L., Pruzan, R., Ma, L., Ouellette, M., Tesmer, V. M., Holt, S. E., Bodnar, A. G., Lichtsteiner, S., Kim, N. W., Trager, J. B., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-498 · Cited by 766
Telomerase activity in human ovarian carcinoma.
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Cited by
Human Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898
Self-citationYuan, X., Larsson, C., & Xu, D. (2019) · Oncogene · doi:10.1038/s41388-019-0872-9 · Cited by 450
Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
Kyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347
Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)
Poole, J. C., Andrews, L. G., & Tollefsbol, T. O. (2001) · Gene · doi:10.1016/s0378-1119(01)00440-1 · Cited by 274
Regulation of the human catalytic subunit of telomerase (hTERT)
Daniel, M., Peek, G. W., & Tollefsbol, T. O. (2012) · Gene · doi:10.1016/j.gene.2012.01.095 · Cited by 266
Metadata
- Authors
- Cong, Y.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-01-01
- Volume
- 8
- Issue
- 1
- Pages
- 137-142
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W1984374449
- Cited by
- 485
- References
- 32
- FWCI
- 13.67
- Type
- journal article
- Language
- en
- Open access
- closed
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