Centro Nacional de Biotecnologia, CSIC, Darwin 3, Campus Universidad Autónoma, Madrid 28049, Spain.
Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1130, New York, NY 10029, USA.
Viruses. 2010 Jan;2(1):298-313. doi: 10.3390/v2010298. Epub 2010 Jan 22.
Tumor suppressor p53 is widely known as 'the guardian of the genome' due to its ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. However, recent studies indicate that p53 is also a direct transcriptional target of type I interferons (IFNs) and thus, it is activated by these cytokines upon viral infection. p53 has been shown to contribute to virus-induced apoptosis, therefore dampening the ability of a wide range of viruses to replicate and spread. Interestingly, recent studies also indicate that several IFN-inducible genes such as interferon regulatory factor 9 (IRF9), IRF5, IFN-stimulated gene 15 (ISG15) and toll-like receptor 3 (TLR3) are in fact, p53 direct transcriptional targets. These findings indicate that p53 may play a key role in antiviral innate immunity by both inducing apoptosis in response to viral infection, and enforcing the type I IFN response, and provide a new insight into the evolutionary reasons why many viruses encode p53 antagonistic proteins.
肿瘤抑制因子 p53 因其能够诱导细胞周期停滞和细胞凋亡从而防止转化细胞的出现而被广泛称为“基因组的守护者”。然而，最近的研究表明，p53 也是 I 型干扰素（IFNs）的直接转录靶标，因此，它会在病毒感染时被这些细胞因子激活。p53 已被证明有助于病毒诱导的细胞凋亡，从而抑制了多种病毒的复制和传播能力。有趣的是，最近的研究还表明，几种 IFN 诱导基因，如干扰素调节因子 9（IRF9）、IRF5、干扰素刺激基因 15（ISG15）和 Toll 样受体 3（TLR3）实际上也是 p53 的直接转录靶标。这些发现表明，p53 可能通过在病毒感染时诱导细胞凋亡以及加强 I 型 IFN 反应来在抗病毒固有免疫中发挥关键作用，并为许多病毒编码 p53 拮抗蛋白的进化原因提供了新的见解。
