Apcher G Sébastien, Heink Sylvia, Zantopf Daniela, Kloetzel Peter-M, Schmid Hans-P, Mayer R John, Krüger Elke
Humboldt Universität zu Berlin, Universitätsklinikum Charité, Institut für Biochemie, Germany.
FEBS Lett. 2003 Oct 9;553(1-2):200-4. doi: 10.1016/s0014-5793(03)01025-1.
The human immunodeficiency virus-1 (HIV-1) Tat protein was previously reported to compete the association of PA28 regulator with the alpha rings of the 20S proteasome and to inhibit its peptidase activity. However, the distinct interaction sites within the proteasome complex remained to be determined. Here we show that HIV-1 Tat binds to alpha4 and alpha7, six beta subunits of the constitutive 20S proteasome and the interferon-gamma-inducible subunits beta2i and beta5i. A Tat-proteasome interaction can also be demonstrated in vivo and leads to inhibition of proteasomal activity. This indicates that Tat can modulate or interfere with cellular proteasome function by specific interaction with distinct proteasomal subunits.
先前有报道称，人类免疫缺陷病毒1型（HIV-1）反式激活因子（Tat蛋白）可竞争PA28调节因子与20S蛋白酶体α环的结合，并抑制其肽酶活性。然而，蛋白酶体复合物内不同的相互作用位点仍有待确定。在此，我们表明HIV-1 Tat可与组成型20S蛋白酶体的α4和α7、六个β亚基以及干扰素γ诱导亚基β2i和β5i结合。Tat与蛋白酶体的相互作用在体内也可得到证实，并导致蛋白酶体活性受到抑制。这表明Tat可通过与不同的蛋白酶体亚基进行特异性相互作用来调节或干扰细胞蛋白酶体功能。
