Namiki Shin, Nakamura Tetsuya, Oshima Shigeru, Yamazaki Motomi, Sekine Yuko, Tsuchiya Kiichiro, Okamoto Ryuichi, Kanai Takanori, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
FEBS Lett. 2005 May 23;579(13):2781-7. doi: 10.1016/j.febslet.2005.04.012. Epub 2005 Apr 20.
An immunoproteasome subunit low molecular weight protein 7 (LMP7) plays critical roles in major histocompatibility complex class I antigen processing; however, the mechanism for its expression has remained unclear. We demonstrate that interferon (IFN) regulatory factor-1 (IRF-1) has a pivotal role in IFN-gamma-dependent LMP7 expression, as was shown for the other two immunosubunits. A tetracycline-inducible system for IRF-1 revealed its function in the LMP7 expression, and a genomic region functionally interacting with IRF-1 was also determined. Furthermore, the role of IRF-1 in IFN-gamma-inducible LMP7 transcription was confirmed by employing small interfering RNA experiments and IRF-1-/- mice. These results suggest that IRF-1 acts as a master regulator for the concerted expression of immunoproteasome components.
免疫蛋白酶体亚基低分子量蛋白7（LMP7）在主要组织相容性复合体I类抗原加工过程中发挥关键作用；然而，其表达机制尚不清楚。我们证明，干扰素（IFN）调节因子-1（IRF-1）在IFN-γ依赖性LMP7表达中起关键作用，其他两个免疫亚基也是如此。用于IRF-1的四环素诱导系统揭示了其在LMP7表达中的功能，还确定了与IRF-1功能相互作用的基因组区域。此外，通过使用小干扰RNA实验和IRF-1基因敲除小鼠，证实了IRF-1在IFN-γ诱导的LMP7转录中的作用。这些结果表明，IRF-1作为免疫蛋白酶体成分协同表达的主要调节因子发挥作用。
