HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition.-猫眼课题宝

HPV 5 和 8 E6 表达会降低 ATM 蛋白水平并减弱 LINE-1 逆转录转座。

DOI：

10.1016/j.virol.2013.04.022

发表时间：

2013

期刊：

Virology

影响因子：

3.7

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Wallace,NicholasA;Gasior,StephenL;Faber,ZacharyJ;Howie,HeatherL;Deininger,PrescottL;Galloway,DeniseA

HPV β 属某些成员（β HPV 5 和 8 E6）的 E6 蛋白表达可以通过降低两种 p53 修饰酶 ATR 和 p300 的稳态水平来破坏 p53 信号传导。在这里，我们证明 β-HPV 5 和 8 E6 还能够降低另一种 p53 修饰酶 ATM 的稳态水平，从而限制 LINE-1 逆转录转座。此外，我们表明 ATM 和 LINE-1 逆转录转座的减少取决于 β-HPV 8 E6 结合和降解 p300 的能力。我们使用抑制剂和显性失活突变体来确认有效的 LINE-1 逆转录转座需要 ATM。此外，在 ATM 缺陷背景中，对 LINE-1 表达的敏感性和 LINE-1 诱导的 DSB 形成都没有改变。总之，这些数据说明了一些 β-HPV 通过促进 p300 降解对 DNA 损伤信号传导产生广泛影响。

The expression of the E6 protein from certain members of the HPV genus β (β HPV 5 and 8 E6) can disrupt p53 signaling by diminishing the steady state levels of two p53 modifying enzymes, ATR and p300. Here, we show that β-HPV 5 and 8 E6 are also capable of reducing the steady state levels of another p53 modifying enzyme, ATM, and as a result restrict LINE-1 retrotransposition. Furthermore, we show that the reduction of both ATM and LINE-1 retrotransposition is dependent upon the ability of β-HPV 8 E6 to bind and degrade p300. We use inhibitors and dominant negative mutants to confirm that ATM is needed for efficient LINE-1 retrotransposition. Furthermore, neither sensitivity to LINE-1 expression nor LINE-1 induced DSB formation is altered in an ATM deficient background. Together, these data illustrate the broad impact some β-HPVs have on DNA damage signaling by promoting p300 degradation.