HPV16 E6 augments Wnt signaling in an E6AP-dependent manner

Hava Lichtig, Daniella Avital Gilboa, Anna Jackman, Pinhas Gonen, Yaara Levav-Cohen, Ygal Haupt, Levana Sherman

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we investigated the effect of HPV16 E6 on the Wnt/β-catenin oncogenic signaling pathway. Luciferase reporter assays indicated that ectopically expressed E6 significantly augmented the Wnt/β-catenin/TCF-dependent signaling response in a dose-dependent manner. This activity was independent of the ability of E6 to target p53 for degradation or bind to the PDZ-containing E6 targets. Epistasis experiments suggested that the stimulatory effect is independent of GSK3β or APC. Coexpression, half-life determination, cell fractionation and immunofluorescence analyses indicated that E6 did not alter the expression levels, stability or cellular distribution of β-catenin. Further experiments using E6 mutants defective for E6AP binding and E6AP knockdown cells indicated the absolute requirement of the ubiquitin ligase E6AP for enhancement of the Wnt signal by E6. Thus, this study suggests a role for the E6/E6AP complex in augmentation of the Wnt signaling pathway which may contribute to HPV induced carcinogenesis.

Original languageEnglish
Pages (from-to)47-58
Number of pages12
JournalVirology
Volume396
Issue number1
DOIs
StatePublished - 5 Jan 2010

Keywords

  • E6
  • E6AP
  • GSK3β
  • HPV
  • TCF
  • Wnt signaling
  • β-Catenin

Fingerprint

Dive into the research topics of 'HPV16 E6 augments Wnt signaling in an E6AP-dependent manner'. Together they form a unique fingerprint.

Cite this