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Basic Characteristics of Mutations
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Mutation Site
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A233G |
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Mutation Site Sentence
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This effect is because 18E6SM harbors an A233G mutation in the donor splicing site that promotes a decrease in the expression of E6*I. |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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E6 |
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Standardized Encoding Gene
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E6
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Genotype/Subtype
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HPV18 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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30322153
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Title
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HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/beta-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor
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Author
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Munoz-Bello JO,Olmedo-Nieva L,Castro-Munoz LJ,Manzo-Merino J,Contreras-Paredes A,Gonzalez-Espinosa C,Lopez-Saavedra A,Lizano M
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Journal
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International journal of molecular sciences
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Journal Info
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2018 Oct 13;19(10):3153
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Abstract
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The Wnt/beta-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/beta-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/beta-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and beta-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with beta-catenin to promote cell proliferation.
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Sequence Data
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-
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