Differential enhancement of a cutaneous HPV promoter by ΔNP63α, Jun and mutant p53
Differential enhancement of a cutaneous HPV promoter by ΔNP63α, Jun and mutant p53
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DOI：
10.4161/cc.4.5.1653
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发表时间：
2005-05-01
期刊：
影响因子：
4.3
通讯作者：
de Villiers, EM
中科院分区：
文献类型：
--
作者：
Fei, JW;Wei, QX;de Villiers, EM
皮肤乳头状瘤病毒引起病变的机制在很大程度上是未知的。Δ Np 63 α同种型的异位表达高度增加了病毒启动子活性。c-Jun的共表达通过与HPV 20 URR的增强子区域中的AP-1位点结合来介导和增加Δ Np 63 α活性。这种由Δ Np 63 α引起的强烈激活在wtp 53存在下减弱，并通过“热点”突变体p53 R248 W的同时表达而消除。我们证明c-Jun通过与Delta Np 63 alpha和wtp 53的直接相互作用负责病毒启动子激活。p53突变体R248 W的下调伴随着Delta Np 63 α和磷酸化c-Jun蛋白水平的降低，本研究中提供的数据提供了一种可能的机制，通过这些细胞蛋白可以调节皮肤乳头瘤病毒基因组，以诱导病毒复制，潜伏感染或恶性转化。
The mechanism through which cutaneous papillomaviruses induce lesions is largely unknown. Ectopic expression of the Delta Np63 alpha isoform highly increased the viral promoter activity. The co-expression of c-Jun mediated and increased the Delta Np63 alpha activity by binding to the AP-1 site in an enhancer region of the HPV 20 URR. This strong activation by Delta Np63 alpha is diminished in the presence of wtp53 and abolished by the simultaneous expression of "hot-spot" mutant p53 R248W. We demonstrate that c-Jun is responsible for the viral promoter activation through its direct interaction with both Delta Np63 alpha and wtp53. The downregulation by p53 mutant R248W is accompanied by reduced protein levels of Delta Np63 alpha and phosphorylated c-Jun. The data presented in this study provide insight into a possible mechanism through which these cellular proteins may modulate a cutaneous papillomavirus genome to induce viral replication, latent infection or malignant transformation.