Seeger M, Ferrell K, Frank R, Dubiel W
Institute of Biochemistry, Humboldt-University, Medical Faculty (Charité), Monbijoustrasse 2A, 10117 Berlin, Germany.
J Biol Chem. 1997 Mar 28;272(13):8145-8. doi: 10.1074/jbc.272.13.8145.
The proteasomal system consists of a proteolytic core, the 20 S proteasome, which associates in an ATP-dependent reaction with the 19 S regulatory complex to form the functional 26 S proteasome. In the absence of ATP, the 20 S proteasome forms a complex with the gamma-interferon-inducible 11 S regulator. Both the 20 S proteasome and the 11 S regulator have been implied in the generation of antigenic peptides. The human immunodeficiency virus (HIV)-1 Tat protein causes a number of different effects during acquired immunodeficiency syndrome (AIDS). Here we show that HIV-1 Tat protein strongly inhibits the peptidase activity of the 20 S proteasome and that it interferes with formation of the 20 S proteasome-11 S regulator complex. In addition, it slightly increases the activity of purified 26 S proteasome. These results may explain the mechanism by which HIV-1-infected cells escape cytotoxic T lymphocyte response and at least in part immunodeficiency in AIDS patients.
蛋白酶体系统由一个蛋白水解核心即20S蛋白酶体组成，它在ATP依赖反应中与19S调节复合物结合形成功能性的26S蛋白酶体。在没有ATP的情况下，20S蛋白酶体与γ干扰素诱导的11S调节因子形成复合物。20S蛋白酶体和11S调节因子都与抗原肽的产生有关。人类免疫缺陷病毒（HIV）-1反式激活蛋白（Tat蛋白）在获得性免疫缺陷综合征（AIDS）期间会产生多种不同的效应。在此我们表明，HIV-1 Tat蛋白强烈抑制20S蛋白酶体的肽酶活性，并干扰20S蛋白酶体-11S调节因子复合物的形成。此外，它还略微增加纯化的26S蛋白酶体的活性。这些结果可能解释了HIV-1感染细胞逃避细胞毒性T淋巴细胞反应以及AIDS患者至少部分免疫缺陷的机制。
