Dao Chinh T, Luo Jiann-Kae, Zhang Dong-Er
Department of Molecular and Experimental Medicine, MEM-L51, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Blood Cells Mol Dis. 2006 May-Jun;36(3):406-13. doi: 10.1016/j.bcmd.2006.02.005. Epub 2006 May 2.
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier that forms conjugates with target protein substrates. As its name suggests, its expression and conjugation to other proteins are highly regulated by interferon (IFN). It was recently demonstrated that ISG15 expression, ISG15 conjugation, and several enzymes involved in ISG15 modification are upregulated in an acute promyelocytic cell line following treatment with retinoic acid, suggesting a possible retinoic acid induced IFN-independent ISG15 modification pathway. In this study, we examined a possible link between IFN signaling and retinoic acid-induced ISG15 conjugation. We observed that ISGylation can be induced by retinoic acid in two myeloid leukemia cell lines. By sandwich ELISA, we detected increased IFN secretion into cell culture media following retinoic acid treatment. Blockade of the type I IFN receptor with a neutralizing antibody blocked retinoic acid induced ISG15 expression and ISG15 conjugation. Taken together, these data suggested that retinoic acid-induced secretion of IFN plays a fundamental role in retinoic acid promoted ISGylation.
干扰素刺激基因15（ISG15）是一种类泛素修饰因子，可与靶蛋白底物形成缀合物。顾名思义，其表达以及与其他蛋白质的缀合受到干扰素（IFN）的高度调控。最近有研究表明，在用视黄酸处理后的急性早幼粒细胞系中，ISG15的表达、ISG15缀合以及几种参与ISG15修饰的酶均上调，这表明可能存在一条视黄酸诱导的不依赖IFN的ISG15修饰途径。在本研究中，我们检测了IFN信号传导与视黄酸诱导的ISG15缀合之间的可能联系。我们观察到视黄酸可在两种髓系白血病细胞系中诱导ISGylation。通过夹心ELISA，我们检测到视黄酸处理后细胞培养基中IFN分泌增加。用中和抗体阻断I型IFN受体可阻断视黄酸诱导的ISG15表达和ISG15缀合。综上所述，这些数据表明视黄酸诱导的IFN分泌在视黄酸促进的ISGylation中起重要作用。
