Interplay of viral and cellular proteins along the long control region of human papillomavirus type 18.
TLDR
The long control region of human genital papillomavirus type 18 harbors transcription regulatory elements, such as the E6 promoter and a cell type-specific enhancer independent of the E2 protein, which could explain its repression by bovine papilloma virus type 1 E2.Abstract:
The long control region of human genital papillomavirus type 18 harbors transcription regulatory elements, such as the E6 promoter and a cell type-specific enhancer independent of the E2 protein. By performing DNase I footprint experiments in vitro with protein extracts from different cell lines and tissues we searched for cellular factors interacting with the totality of the control region. We detected a total of eight different protected sites; most of them were found with all the extracts. Two of these sites, one in the enhancer and the other in the sequences proximal to the E6 cap site, interact with a member of the activator protein 1 family. However, in the absence of fine mutational analysis, we cannot readily discern an exact functional role for the different binding sites. We also characterized two regions, which are protected only in the presence of E2, corresponding to the perfect palindromes ACCGN4CGGT and present either 500 nucleotides or tandemly repeated about 70 nucleotides upstream of the E6 cap site. This last protected area covers a large part of the putative TATA box of the E6 promoter and could explain its repression by bovine papilloma virus type 1 E2, which could interfere with binding of the TFII D ubiquitous transcription factor to the TATA sequence of the promoter.read more
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Book ChapterDOI
Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types.
TL;DR: The DNAs of the first cervical cancer-associated human papillomavirus (HPV) types were cloned and characterized and are regularly and frequently found in biopsies obtained from cervical cancer patients throughout the world.
Journal ArticleDOI
Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters.
TL;DR: E2-mediated repression of HPV-18 P105 promoter activity was shown to be a transcriptional effect and the interaction of E2 with promoter-proximal E2-binding sites is likely to be important for the controlled expression of viral genes transcribed from the HPV-16 P97 promoter and the HPV in infected human genital epithelial cells.
Journal ArticleDOI
CpG Methylation of Human Papillomavirus Type 16 DNA in Cervical Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation Correlates with Carcinogenic Progression
Vinay Badal,Linda S. H. Chuang,Eileen Hwee-Hong Tan,Sushma Badal,Luisa L. Villa,Cosette M. Wheeler,Benjamin F. L. Li,Hans-Ulrich Bernard +7 more
TL;DR: It is reported that HPV genomes are efficiently targeted in vivo by CpG methylation, a well-known mechanism of transcriptional repression, and opens research on the importance of this mechanism during the viral life cycle, and provides a marker relevant for the etiology and diagnosis of cervical cancer.
Journal ArticleDOI
The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets
TL;DR: Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6 /E7 but evade senescence through hypoxia-induced mTOR impairment, and prospective E6-E7 inhibitors may benefit from a combination with treatment strategies directed against hypoxic tumor cells.
Journal ArticleDOI
Expression of the papillomavirus E2 protein in HeLa cells leads to apoptosis.
TL;DR: The results suggest that the effects of E2 on cell cycle progression and cell death follow distinct pathways involving two different functions of p53.
References
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TL;DR: The data indicate that HPV 16 DNA prevails in malignant tumors, rendering an accidental contamination with papillomavirus DNA from adjacent papillomas rather unlikely, and suggests a dependence of HPV 16 replication on helper virus.
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Structure and transcription of human papillomavirus sequences in cervical carcinoma cells
Elisabeth Schwarz,U K Freese,Lutz Gissmann,Wolfgang Mayer,Birgit Roggenbuck,Armin Stremlau,Harald zur Hausen +6 more
TL;DR: It is found that the HPV 18 DNA is integrated into the cellular genome and is amplified in HeLa and 756 cells, and some of the transcripts are composed of HPV 18 and cellular sequences.
Journal ArticleDOI
A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.
TL;DR: DNA of a new papillomavirus type was cloned from a cervical carcinoma biopsy and the data reveal that the DNA might be integrated into the host cell genome, which is tentatively proposed to be HPV 18.