Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liege, Liege, Belgium.
Mol Immunol. 2010 Nov-Dec;48(1-3):119-27. doi: 10.1016/j.molimm.2010.09.004. Epub 2010 Oct 13.
Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated.
凋亡和细胞周期阻滞的锌指蛋白调节因子（Zac1）是一种转录因子，能够通过独立的途径诱导细胞凋亡或细胞周期阻滞。尽管 Zac1 具有重要的潜在功能，但人们对其生理调节和生物学功能知之甚少。我们发现，在经过聚肌苷酸-聚胞苷酸[poly(I:C)]处理的鼠胚胎成纤维细胞（MEFs）中表达了变体 Zac1b，poly(I:C) 是一种合成的双链 RNA。这种调节主要通过 Toll 样受体 3（TLR3）和干扰素调节因子 3（IRF3）依赖性途径发生。由于 TLR3 和 IRF3 是抗病毒免疫的核心激活剂，我们假设 Zac1 可能参与抗病毒反应。与这一观点一致，我们观察到 Zac1b 在感染脑炎心肌炎病毒（EMCV）的 MEFs 中表达。我们还观察到 Zac1 缺陷型 MEFs 对 EMCV 诱导的细胞死亡的敏感性低于野生型 MEFs。然而，Zac1 基因失活对感染 EMCV 的小鼠的存活没有影响。总之，本研究首次描述了 Zac1b 的转录调控，该调控由合成 dsRNA 和 RNA 病毒诱导，其功能意义仍有待进一步研究。
