p53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T-antigen
p53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T-antigen
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DOI：
10.1006/viro.1996.0241
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发表时间：
1996-05-01
期刊：
影响因子：
3.7
通讯作者：
Grummt, F
中科院分区：
文献类型：
--
作者：
Staib, C;Pesch, J;Grummt, F
DNA复制的开始是人类嗜神经性多瘤病毒JC生命周期中的重要步骤。在这份报告中，证据表明，人类和小鼠肿瘤抑制蛋白p53强烈抑制JCV DNA复制在体内。这种抑制是剂量依赖性的，而不是响应于p53的JCV大T抗原表达降低的继发效应。使用小鼠p53的缺失突变体和人p53的肿瘤源性点突变，剖析了p53抑制JCV DNA复制的基础。小鼠p53的氨基或羧基末端结构域的缺失不干扰JCV DNA复制的抑制。然而，删除高度保守的p53中心区域取消了对复制的抑制作用。肿瘤来源的人突变体p53（His 273）显著抑制JCV DNA复制，而另一种致瘤突变体p53（His 175）则无抑制作用。同时，p53和JCV大T抗原之间的直接蛋白质-蛋白质相互作用在不影响JCV DNA复制的突变体中丢失。这些结果有力地表明，p53通过与JCV大T抗原相互作用来抑制JCV DNA复制。(C)出版社：Academic Press，Inc.
The onset of DNA replication is an important step within the life cycle of the human neurotropic polyomavirus JC. In this report, evidence that both the human and the murine tumor suppressor protein p53 strongly inhibit JCV DNA replication in vivo is presented. This inhibition is dose-dependent and not a secondary effect of a decreased expression of JCV large T-antigen in response to p53. Using deletion mutants of murine p53 and tumor-derived point mutations of human p53, the basis of the suppression of JCV DNA replication by p53 was dissected. Deletion of either the amino- or the carboxy-terminal domain of murine p53 did not interfere with the repression of JCV DNA replication. However, deletion of the highly conserved central region of p53 abolished the inhibitory effect on replication. The tumor-derived human mutant p53(His273) inhibited JCV DNA replication significantly, whereas another tumorigenic mutant, p53(His175), had no inhibitory effect. Concomitantly, a direct protein-protein interaction between p53 and JCV large T-antigen was lost in mutants which did not affect JCV DNA replication. These results strongly suggest that p53 inhibits JCV DNA replication by interacting with JCV large T-antigen. (C) 1996 Academic Press, Inc.