Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Whether the nuclei of iPS cells are truly rejuvenated or whether they might retain some of the marks of aging from the cells from which they were derived is a major question.
Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells
- T. Kiyono, S. Foster, J. I. Koop, J. McDougall, D. Galloway, A. Klingelhutz
- 5 November 1998
It is found that neither addition of hTERT nor induction of telomerase activity by E6, both of which are active in maintaining telomere length, results in immortalization, and inactivation of the Rb/p16 pathway by E7 or downregulation of p16 expression, in combination with telomersase activity, is able to immortalize epithelial cells efficiently.
Telomerase activation by the E6 gene product of human papillomavirus type 16
It is shown that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells, indicating that telomerases activation is an intrinsic, but insufficient, component of transformation by HPV.
Development of cystic fibrosis and noncystic fibrosis airway cell lines.
The reverse transcriptase component of telomerase, hTERT, and human papillomavirus type 16 (HPV-16) E6 and E7 genes are utilized to transform normal and cystic fibrosis human airway epithelial (HAE) cells to serve as models for studying ion physiology, therapeutic intervention for CF, and innate immunity.
Enhanced radiation sensitivity in HPV-positive head and neck cancer.
These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC, and suggest that low levels of normally functioning p53 in HPV+, which could be activated by radiation, leading to cell death.
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
It is demonstrated that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting telomerase, and it is shown that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
Papillomavirus E6 oncoproteins.
HPV16‐E6 associated hTERT promoter acetylation is E6AP dependent, increased in later passage cells and enhanced by loss of p300
The E6 oncoprotein from high‐risk HPV types activates human telomerase reverse transcriptase (hTERT) transcription in human keratinocytes. Studies on how E6 regulates hTERT have implicated E‐box or…
Cigarette smoke induces cellular senescence.
- T. Nyunoya, M. Monick, A. Klingelhutz, T. Yarovinsky, J. Cagley, G. Hunninghake
- Medicine, BiologyAmerican Journal of Respiratory Cell and…
- 13 July 2006
Observations suggest that while a single exposure to cigarette smoke inhibits normal fibroblast proliferation (required for lung repair), multiple exposures tocigarette smoke move cells into an irreversible state of senescence, which may be an essential feature of emphysema.
Epstein-Barr Virus Latent Membrane Protein 2A Activates β-Catenin Signaling in Epithelial Cells
It is shown that EBV LMP2A activates the PI3K and β-catenin signaling pathways in telomerase-immortalized human foreskin keratinocytes (HFK) and the Wnt pathway is inappropriately activated in 90% of colon cancers and is dysregulated in several other cancers, and these data suggest that activation of this pathway by L MP2A may contribute to the generation of EBV-associated cancers.