HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/ß-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor.
Int J Mol Sci
; 19(10)2018 Oct 13.
Article
en En
| MEDLINE
| ID: mdl-30322153
ABSTRACT
The Wnt/ß-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/ß-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/ß-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 ß-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 ß-catenin to promote cell proliferation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Neoplasias del Cuello Uterino
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Proteínas Oncogénicas Virales
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Proteínas de Unión al ADN
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Papillomavirus Humano 18
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Factor de Transcripción 4
Límite:
Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
México