Grimm L M, Goldberg A L, Poirier G G, Schwartz L M, Osborne B A
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
EMBO J. 1996 Aug 1;15(15):3835-44.
Cell death in many different organisms requires the activation of proteolytic cascades involving cytosolic proteases. Here we describe a novel requirement in thymocyte cell death for the 20S proteasome, a highly conserved multicatalytic protease found in all eukaryotes. Specific inhibitors of proteasome function blocked cell death induced by ionizing radiation, glucocorticoids or phorbol ester. In addition to inhibiting apoptosis, these signals prevented the cleavage of poly(ADP-ribose) polymerase that accompanies many cell deaths. Since overall rates of protein degradation were not altered significantly during cell death in thymocytes, these results suggest that the proteasome may either degrade regulatory protein(s) that normally inhibit the apoptotic pathway or may proteolytically activate protein(s) than promote cell death.
许多不同生物体中的细胞死亡都需要激活涉及胞质蛋白酶的蛋白水解级联反应。在此，我们描述了20S蛋白酶体在胸腺细胞死亡中的一种新需求，20S蛋白酶体是一种在所有真核生物中都存在的高度保守的多催化蛋白酶。蛋白酶体功能的特异性抑制剂可阻断电离辐射、糖皮质激素或佛波酯诱导的细胞死亡。除了抑制细胞凋亡外，这些信号还阻止了伴随许多细胞死亡的聚（ADP-核糖）聚合酶的裂解。由于胸腺细胞在细胞死亡过程中蛋白质降解的总体速率没有显著改变，这些结果表明蛋白酶体可能降解通常抑制凋亡途径的调节蛋白，或者可能通过蛋白水解激活促进细胞死亡的蛋白。
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