The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints.
The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints.
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DOI：
10.1016/j.virol.2009.10.051
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发表时间：
2010-02-05
期刊：
影响因子：
3.7
通讯作者：
Chen JJ
中科院分区：
文献类型：
--
作者：
Zhang W;Li J;Kanginakudru S;Zhao W;Yu X;Chen JJ
HPV 58型（HPV-58）是东亚宫颈癌中第三常见的HPV类型，但对其如何促进致癌作用知之甚少。在这项研究中，我们证明了HPV-58 E7显着促进增殖，并延长原代人角质形成细胞（PHK）的寿命。HPV-58 E7废除了G1有丝分裂后检查点，尽管效率低于HPV-16 E7。与这些观察结果一致，HPV-58 E7下调细胞肿瘤抑制因子pRb的程度低于HPV-16 E7。与表达HPV-16 E7的PHK类似，尽管存在升高水平的p53和p21，Cdk 2在表达HPV-58 E7的PHK中仍保持活性。有趣的是，HPV-58 E7比HPV-16 E7更有效地下调p130。我们的研究表明，下调pRb/p130和废除细胞周期检查点的HPV-58 E7的能力之间的相关性，这也与HPV-58感染相关的宫颈癌进展的生物学风险。
HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrated that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.
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