Comparison of p53 and the PDZ domain containing protein MAGI-3 regulation by the E6 protein from high-risk human papillomaviruses.
Comparison of p53 and the PDZ domain containing protein MAGI-3 regulation by the E6 protein from high-risk human papillomaviruses.
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DOI：
10.1186/1743-422x-5-67
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发表时间：
2008-06-02
期刊：
影响因子：
4.8
通讯作者：
Matlashewski G
中科院分区：
文献类型：
--
作者：
Ainsworth J;Thomas M;Banks L;Coutlee F;Matlashewski G
人乳头瘤病毒（hpv）引起的细胞转化的核心是E6蛋白靶向细胞p53和含有PDZ结构域的蛋白（包括MAGI-3）进行降解的能力。本研究的目的是在平行实验条件下比较e6介导的p53和MAGI-3的降解，并进一步研究蛋白酶体和泛素化的参与。我们还比较了几种HPV类型（包括HPV-33的不同变体）中E6对p53和MAGI-3的降解。来自不同HPV类型的所有E6基因在介导p53和MAGI-3的降解方面表现出相似的能力，尽管在不同的33E6变体中可能存在细微的差异。然而，E6介导的p53和MAGI-3的降解存在差异。蛋白酶体抑制试验部分保护p53免受E6介导的降解，但对MAGI-3没有保护作用。此外，在体内p53被E6和MDM2泛素化的情况下，没有检测到MAGI-3的泛素化。这些结果表明，尽管p53和MAGI-3都是致癌性E6的有效靶点，但E6介导p53和MAGI-3降解的机制在蛋白酶体降解之前的泛素化参与方面是不同的。
Central to cellular transformation caused by human papillomaviruses (HPVs) is the ability of E6 proteins to target cellular p53 and proteins containing PDZ domains, including MAGI-3, for degradation. The aim of this study was to compare E6-mediated degradation of p53 and MAGI-3 under parallel experimental conditions and further with respect to the involvement of proteasomes and ubiquitination. We also compared the degradation of p53 and MAGI-3 by E6 from several HPV types including different variants from HPV-33. All of the E6 genes from different HPV types displayed similar abilities to mediate the degradation of both p53 and MAGI-3 although there may be subtle differences observed with the different 33E6 variants. There were however differences in E6 mediated degradation of p53 and MAGI-3. Proteasome inhibition assays partially protected p53 from E6 mediated degradation, but did not protect MAGI-3. In addition, under conditions where p53 was ubiquitinated by E6 and MDM2 in vivo, ubiquitination of MAGI-3 was not detected. These results imply that although both p53 and MAGI-3 represent effective targets for oncogenic E6, the mechanisms by which E6 mediates p53 and MAGI-3 degradation are distinct with respect to the involvement of ubiquitination prior to proteasomal degradation.