The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Telomerase activation by the E6 gene product of human papillomavirus type 16
Abstract
Activation of telomerase, a ribonucleoprotein complex that synthesizes telomere repeat sequences, is linked to cell immortalization and is characteristic of most cell lines and tumours. Here we show that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells. This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6. Studies using HPV-16 E6 mutants showed that there was no correlation between the ability of the mutants to activate telomerase and their ability to target p53 for degradation, suggesting that telomerase activation by HPV-16 E6 is p53 independent. Keratinocytes expressing wild-type HPV-16 E6 have an extended lifespan, but do not become immortal, indicating that telomerase activation and E6-mediate degradation of p53 are insufficient for their immortalization. These results show that telomerase activation is an intrinsic, but insufficient, component of transformation by HPV.
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In the citing paper
“Studies of mutated E6 proteins reveal that induction of telomerase is an independent function of E6 separable from p53 degradation and that telomerase activation rather than p53 degradation is the critical step for immortalization of epithelial cells (Klingelhutz et al. 1996; Kiyono et al. 1998).”
From Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex (2004) · cites this paper as Klingelhutz et al. 1996
In the citing paper
“Previous data have indicated that induction of hTERT by HPV-16 E6 may involve epigenetic phenomenon such as histone acetylation or chromatin remodeling (Klingelhutz et al. 1996; Kiyono et al. 1998; Baege et al. 2002).”
From Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex (2004) · cites this paper as Klingelhutz et al. 1996
In the citing paper
“Furthermore, hTERT induction and p53 degradation are separable and distinct functions of E6 as indicated by E6 mutants such as F2V, 8S/9A/10T, and Y54H that can activate telomerase but do not target p53 for degradation (Table 1; Klingelhutz et al. 1996; Liu et al. 1999).”
From Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex (2004) · cites this paper as Klingelhutz et al. 1996
In the citing paper
“In HPV-mediated cancers, high-risk E6 proteins can activate telomerase in association with E6AP, and this was shown to be critical for immortalization [246,247]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [246]
Citations
Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495
Greider, C. W., & Blackburn, E. H. (1987) · Cell · doi:10.1016/0092-8674(87)90576-9 · Cited by 1,150
Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04990.x · Cited by 879
Telomerase activity in human ovarian carcinoma.
Counter, C. M., Hirte, H. W., Bacchetti, S., & Harley, C. B. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.2900 · Cited by 677
In vivo loss of telomeric repeats with age in humans
Lindsey, J., McGill, N. I., Lindsey, L. A., Green, D. K., & Cooke, H. J. (1991) · Mutation Research/DNAging · doi:10.1016/0921-8734(91)90032-7 · Cited by 463
Research works printed but not linked: 12
- Blackburn, E. H. A. Rev. Biochem. 61, 113–129 (1992). · DOI
- Chadeneau, C., Hay, K., Hirte, H. W., Gallinger, S. & Bacchetti, S. Cancer Res. 55, 2533–2536 (1995).
- Klingelhutz, A. J., Barber, S. A., Smith, P. P., Dyer, K. & McDougall, J. K. Molec. cell. Biol. 14, 961–969 (1994). · DOI · Paper page
- Allsopp, R. C. et al. Proc. natn. Acad. Sci. U.S.A. 89, 10114–10118 (1992). · DOI · Paper page
- Hastie, N. D. et al. Nature 346, 866–868 (1990). · DOI · Paper page
- Levy, M. Z., Allsopp, R. C., Futcher, A. B., Greider, C. W. & Harley, C. B. J. molec. Biol. 225, 951–960 (1992). · DOI · Paper page
- Harley, C. B. Mutat. Res. 256, 271–282 (1991). · DOI · Paper page
- Halbert, C. L., Demers, G. W. & Galloway, D. A. J. Virol. 65, 473–478 (1991). · DOI · Paper page
- Miller, A. D., Bender, M. A., Harris, E. A., Kaleko, M. & Gelinas, R. E. J. Virol. 62, 4337–4345 (1988). · DOI
- Foster, S. A., Demers, G. W., Etscheid, B. G. & Galloway, D. A. J. Virol. 68, 5698–5705 (1994). · DOI · Paper page
- Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. & Howley, P. M. Cell 63, 1129–1136 (1990). · DOI · Paper page
- Broccoli, D., Young, J. W. & Delange, T. Proc. natn. Acad. Sci. U.S.A. 92, 9082–9086 (1995). · DOI · Paper page
Cited by
Meyerson, 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
Bryan, T. M., Englezou, A., Dalla-Pozza, L., Dunham, M. A., & Reddel, R. R. (1997) · Nature Medicine · doi:10.1038/nm1197-1271 · Cited by 1,292
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206
Self-citationMolecular biology of human papillomavirus infection and cervical cancer
Doorbar, J. (2006) · Clinical Science · doi:10.1042/cs20050369 · Cited by 1,072
Disruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044
Metadata
- Authors
- Klingelhutz, A. J., Foster, S. A., & McDougall, J. K.
- Venue
- Nature
- Published
- 1996-03
- Volume
- 380
- Issue
- 6569
- Pages
- 79-82
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 660
- References
- 9
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- Klingelhutz, A. J., Foster, S. A., & McDougall, J. K. (1996). Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. https://doi.org/10.1038/380079a0
