Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition.
Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition.
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发表时间：
1999-08
期刊：
影响因子：
11.2
通讯作者：
R. Batchu;M. Shammas;J. Y. Wang;Nikhil C. Munshi
中科院分区：
文献类型：
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作者：
R. Batchu;M. Shammas;J. Y. Wang;Nikhil C. Munshi
腺相关病毒（AAV）是一种非致病性的单链DNA病毒，属于细小病毒科。AAV对腺病毒（一种DNA肿瘤病毒）的抑癌特性已被充分证实。Rep78是AAV的主要调控蛋白，被认为是其抗原性的主要原因。大多数DNA肿瘤病毒通过破坏p53的功能来干扰细胞周期通路。在这里，我们提出证据，证明AAV通过保护腺病毒介导的p53降解而作为抗腺病毒的抗增殖剂，这一点得到了Western blot分析和抗p53抗体免疫沉淀分析的证实。共免疫沉淀实验显示AAV Rep78在体内与p53物理结合。此外，纯化的p53与AAV Rep78亲和柱的结合证实了它们之间的相互作用。这些结果首次证明AAV对腺病毒的抗增殖作用至少部分是通过AAV Rep78与p53的相互作用介导的。
Adeno-associated virus (AAV) is a nonpathogenic, single-stranded DNA virus belonging to the parvoviridae family. Onco-suppressive properties of AAV against adenovirus, a DNA tumor virus, have been well documented. Rep78, a major regulatory protein of AAV, is believed to be responsible for its antioncogenic properties. Most DNA tumor viruses disturb the cell cycle pathways by essentially abrogating the functions of p53. Here we present evidence that AAV acts as an antiproliferative agent against adenovirus by protecting the adenoviral-mediated degradation of p53 as confirmed by both Western blot analysis and immunoprecipitation analysis with anti-p53 antibody. Coimmunoprecipitation experiments revealed that the AAV Rep78 is physically bound to p53 in vivo. Furthermore, the binding of purified p53 to the AAV Rep78 affinity column confirms their interaction. These results document for the first time that the antiproliferative effects of AAV against adenovirus are mediated, at least in part, by the interaction of AAV Rep78 with p53.