Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis
Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis
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DOI：
10.1128/jvi.76.6.2692-2702.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Lambert, P
中科院分区：
文献类型：
--
作者：
Greenway, AL;McPhee, DA;Lambert, P
人类免疫缺陷病毒I型（HIV-1）的nef基因产物对于诱导AIDS是重要的，并且其功能的关键在于其通过靶向细胞信号转导蛋白操纵T细胞功能的能力。我们报道了Nef共沉淀来自细胞的多蛋白复合物，该复合物含有肿瘤抑制蛋白p53。我们现在发现Nef直接与p53相互作用。结合实验表明Nef的N端57个残基片段（Nef 1-57）含有p53结合结构域。Nef在HIV-1感染过程中也与p53相互作用。由于p53在细胞凋亡的调节中起着关键作用，我们假设Nef可能改变这一过程。Nef抑制MOLT-4细胞中UV光诱导的p53依赖性凋亡，Nef 1-57与其全长对应物一样有效。Nef对p53凋亡功能的抑制很可能是由于其观察到的降低p53蛋白半衰期的能力，从而降低p53 DNA结合活性和转录激活。这些数据表明，HIV-1 Nef可能通过阻断p53介导的细胞凋亡延长感染细胞的生存力来增强HIV复制。
The nef gene product of human immunodeficiency virus type I (HIV-1) is important for the induction of AIDS, and key to its function is its ability to manipulate T-cell function by targeting cellular signal transduction proteins. We reported that Nef coprecipitates a multiprotein complex from cells which contains tumor suppressor protein p53. We now show that Nef interacts directly with p53. Binding assays showed that an N-terminal, 57-residue fragment of Nef (Nef 1-57) contains the p53-binding domain. Nef also interacted with p53 during HIV-1 infection in vitro. As p53 plays a critical role in the regulation of apoptosis, we hypothesized that Nef may alter this process. Nef inhibited UV light-induced, p53-dependent apoptosis in MOLT-4 cells, with Nef 1-57 being as effective as its full-length counterpart. The inhibition by Nef of p53 apoptotic function is most likely due its observed ability to decrease p53 protein half-life and, consequently, p53 DNA binding activity and transcriptional activation. These data show that HIV-1 Nef may augment HIV replication by prolonging the viability of infected cells by blocking p53-mediated apoptosis.