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RSS FeedsIJMS, Vol. 19, Pages 3153: HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/?-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor (International Journal of Molecular Sciences)

 
 

13 october 2018 16:00:27

 
IJMS, Vol. 19, Pages 3153: HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/?-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor (International Journal of Molecular Sciences)
 




The Wnt/β-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/β-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/β-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 β-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 β-catenin to promote cell proliferation.


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13 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 19, Pages 3154: Relationship between the Regulation of Caspase-8-Mediated Apoptosis and Radioresistance in Human THP-1-Derived Macrophages (International Journal of Molecular Sciences)
IJMS, Vol. 19, Pages 3151: Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats (International Journal of Molecular Sciences)
 
 
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