Oncogene Proteins, Viral

Publication Title: 
Oncogene

Cell cycle checkpoints and tumor suppressor gene functions appear to be required for the maintenance of a stable genome in proliferating cells. In this study chromosomal destabilization was monitored in relation to telomere structure, lifespan control and G2 checkpoint function. Replicative senescence was inactivated in secondary cultures of human skin fibroblasts by expressing the human papillomavirus type 16 (HPV-16) E6 oncoprotein to inactivate p53. Chromosome aberrations were enumerated during in vitro aging of isogenic control (F5neo) and HPV-16E6-expressing (F5E6) fibroblasts.

Author(s): 
Filatov, L.
Golubovskaya, V.
Hurt, J. C.
Byrd, L. L.
Phillips, J. M.
Kaufmann, W. K.
Publication Title: 
Bioscience, Biotechnology, and Biochemistry

Transfection of nearly senesced human fibroblasts with plasmids encoding HPV16 E6 protein or dominant-negative p53 mutants greatly increased their colony-forming ability. Isolated colonies with these plasmids showed extension of lifespan compared to those with a control plasmid. These data demonstrate that p53 plays a major role in senescence in normal human fibroblasts.

Author(s): 
Ide, A.
Fujii, M.
Nakababashi, K.
Ayusawa, D.
Publication Title: 
Oncogene

Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway.

Author(s): 
Morris, Mark
Hepburn, Peter
Wynford-Thomas, David
Publication Title: 
Journal of Virology

Human papillomaviruses (HPVs) belonging to the Betapapillomavirus genus have recently been implicated in squamous cell carcinomas of the skin, though the mechanisms by which they initiate carcinogenesis are unclear. We show that human foreskin keratinocytes (HFKs) expressing several betapapillomavirus E6 (beta-E6) proteins display life span extension, but not to the extent seen in HFKs expressing HPV type 16 E6 (16E6). Additionally, we demonstrate that beta-E6 proteins can differentially activate telomerase.

Author(s): 
Bedard, Kristin M.
Underbrink, Michael P.
Howie, Heather L.
Galloway, Denise A.
Publication Title: 
Experimental Dermatology

Dyskeratosis congenita (DC) is characterized by the triad of reticulate skin pigmentation, nail dystrophy and leukoplakia. Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients. DC is caused by mutations in genes encoding for telomerase complex factors. Although there is an association of epidermal abnormalities with DC, epidermal cells from DC donors have not been previously characterized.

Author(s): 
Gourronc, Francoise A.
Robertson, mckaylee M.
Herrig, Annie K.
Lansdorp, Peter M.
Goldman, Frederick D.
Klingelhutz, Aloysius J.
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