The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function
The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function
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DOI：
10.1073/pnas.94.4.1206
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Dobner, T
中科院分区：
文献类型：
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作者：
Nevels, M;Rubenwolf, S;Dobner, T
我们最近发现5型腺病毒E4 orf 6蛋白与细胞肿瘤抑制蛋白p53相互作用并阻断p53的转录功能。在这里，我们报告，E4 orf 6蛋白可以促进原代啮齿动物上皮细胞的焦点形成与腺病毒E1 A和E1 A加上E1 B蛋白的合作。E4 orf 6蛋白还可以抑制p53介导的对E1 A加E1 B-19 kDa诱导的病灶形成的抑制。E4 orf 6蛋白的突变体分析表明，这些活动与腺病毒蛋白在瞬时转染试验中缓解p53羧基末端区域介导的转录抑制的能力相关。我们进一步证明了野生型E4 orf 6的表达与转化大鼠细胞中p53稳态水平的显著降低相关。我们的数据表明，腺病毒5型编码两种不同的蛋白质，E1 B-55 kDa和E4 orf 6，结合p53，并有助于通过调节p53转录功能的转化。
We have recently shown that the adenovirus type 5 E4orf6 protein interacts with the cellular tumor suppressor protein p53 and blocks p53 transcriptional functions. Here we report that the E4orf6 protein can promote focus formation of primary rodent epithelial cells in cooperation with adenovirus E1A and E1A plus E1B proteins. The E4orf6 protein can also inhibit p53-mediated suppression of E1A plus E1B-19kDa-induced focus formation. Mutant analysis of the E4orf6 protein demonstrates that these activities correlate with the ability of the adenovirus protein to relieve transcriptional repression mediated by the carboxyl-terminal region of p53 in transient transfection assays. We further demonstrate that expression of wild-type E4orf6 correlates with a dramatic reduction of p53 steady-state levels in transformed rat cells. Our data demonstrate that adenovirus type 5 encodes two different proteins, E1B-55kDa and E4orf6, that bind to p53 and contribute to transformation by modulating p53 transcriptional functions.