HPV16 E6 augments Wnt signaling in an E6AP-dependent manner
HPV16 E6 augments Wnt signaling in an E6AP-dependent manner
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DOI：
10.1016/j.virol.2009.10.011
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发表时间：
2010-01-05
期刊：
影响因子：
3.7
通讯作者：
Sherman, Levana
中科院分区：
文献类型：
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作者：
Lichtig, Hava;Gilboa, Daniella Avital;Sherman, Levana
在这项研究中，我们研究了HPV 16 E6对Wnt/β-catenin致癌信号通路的影响。荧光素酶报告基因分析表明，异位表达的E6显着增强Wnt/β连环蛋白/TCF依赖的信号转导反应的剂量依赖性的方式。这种活性不依赖于E6靶向p53降解或结合含PDZ的E6靶标的能力。上位性实验表明，刺激作用不依赖于GSK 3 β或APC。共表达、半衰期测定、细胞分级分离和免疫荧光分析表明，E6没有改变β-连环蛋白的表达水平、稳定性或细胞分布。使用E6 AP结合缺陷的E6突变体和E6 AP敲低细胞的进一步实验表明，E6增强Wnt信号绝对需要泛素连接酶E6 AP。因此，这项研究表明E6/E6 AP复合物在增强Wnt信号通路中的作用，这可能有助于HPV诱导的致癌作用。(C)2009 Elsevier Inc. All rights reserved.
In this study we investigated the effect of HPV16 E6 on the Wnt/beta-catenin oncogenic signaling pathway. Luciferase reporter assays indicated that ectopically expressed E6 significantly augmented the Wnt/beta 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 GSK3 beta 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 beta-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. (C) 2009 Elsevier Inc. All rights reserved.