Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner
Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner
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DOI：
10.1074/jbc.m109113200
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发表时间：
2002-01-25
影响因子：
4.8
通讯作者：
Choe, JH
中科院分区：
文献类型：
--
作者：
Hwang, SG;Lee, DY;Choe, JH
人乳头瘤病毒(HPV)E7癌蛋白可以使原代人类细胞永生化，并诱导肿瘤形成。E7的这些特性依赖于其抑制视网膜母细胞瘤蛋白(PRB)活性的能力，而PRB又影响E2F功能。E2F蛋白调控与分化、发育、细胞增殖和凋亡相关的基因表达。通过遗传和生化方法，本研究表明E7在体内和体外都与E2F1结合，两种蛋白共同定位在细胞核中。重要的是，高危组HPVE7与E2F1的结合比低危组HPVE7与E2F1的结合更紧密。高危组的E7能强烈激活C33A或293T细胞中依赖于E2F1的转录，而低危组的E7只能微弱地激活转录。通过凝胶迁移率改变分析，我们还发现E7与E2F1-DNA复合物结合。此外，通过使用不能与pRb结合的E7和E2F1突变体，我们证明了E7的这些活性不依赖于pRb。综上所述，这些数据表明，E7有助于解除对依赖于pRb的E2F1抑制的调控，并进一步激活不依赖pRb的E2F1。
The human papillomavirus (HPV) E7 oncoprotein can immortalize primary human cells and induce tumor formation. These properties of E7 depend on its ability to inhibit the activity of retinoblastoma protein (pRB), which in turn affects E2F function. E2F proteins control the expression of genes involved in differentiation, development, cell proliferation, and apoptosis. By using genetic and biochemical approaches, the present study shows that E7 binds to E2F1 in vivo and in vitro and that both proteins co-localize in the nucleus. Importantly, the binding of the high risk group HPV E7 to E2F1 is tighter than the binding of the low risk group HPV E7 to E2F1. Although E7 of the high risk group HPVs activates E2F1-dependent transcription strongly in C33A or 293T cells, E7 of the low risk group HPVs activates transcription only weakly. By using electrophoretic mobility shift assay, we also showed that E7 binds to E2F1-DNA complexes. Furthermore, we show that these activities of E7 are independent of pRB by using E7 and E2F1 mutants that cannot bind to pRB. Taken together, these data suggest that E7 contributes to the deregulation of pRB-dependent E2F1 repression and to the further activation of E2F1 independently of pRB.