Yonsei University, Division of Biological Science and Technology, Wonju 220-100, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):926-30. doi: 10.1016/j.bbrc.2009.11.166. Epub 2009 Dec 4.
Interferon regulatory factor-1 (IRF-1) is an interferon-induced transcriptional activator that suppresses tumors by impeding cell proliferation. Recently, we demonstrated that the level of SUMOylated IRF-1 is elevated in tumor cells, and that SUMOylation of IRF-1 attenuates its tumor-suppressive function. Here we report that SUMOylated IRF-1 mimics IRF-2, an antagonistic repressor, and shows oncogenic potential. To demonstrate the role of SUMOylated IRF-1 in tumorigenesis, we used SUMO-IRF-1 recombinant protein. Stable expression of SUMO-IRF-1 in NIH3T3 cells resulted in focus formation and anchorage-independent growth in soft agar. Inoculation of SUMO-IRF-1-transfected cells into athymic nude mice resulted in tumor formation and infiltration of adipose tissues. Finally, we demonstrated that SUMO-IRF-1 transforms NIH3T3 cells in a dose-dependent manner suggesting that SUMOylated IRF-1 may act as an oncogenic protein in tumor cells.
干扰素调节因子-1（IRF-1）是一种干扰素诱导的转录激活因子，通过抑制细胞增殖来抑制肿瘤。最近，我们证明肿瘤细胞中 SUMO 化的 IRF-1 水平升高，IRF-1 的 SUMO 化减弱了其肿瘤抑制功能。在这里，我们报告说 SUMO 化的 IRF-1 模拟了 IRF-2，一种拮抗的抑制剂，并表现出致癌潜力。为了证明 SUMO 化的 IRF-1 在肿瘤发生中的作用，我们使用了 SUMO-IRF-1 重组蛋白。稳定表达 SUMO-IRF-1 的 NIH3T3 细胞导致焦点形成和软琼脂中的锚定非依赖性生长。将 SUMO-IRF-1 转染的细胞接种到无胸腺裸鼠中导致肿瘤形成和脂肪组织浸润。最后，我们证明 SUMO-IRF-1 以剂量依赖性方式转化 NIH3T3 细胞，表明 SUMO 化的 IRF-1 可能在肿瘤细胞中作为致癌蛋白发挥作用。
