Papapostolou David, Reboud-Ravaux Michèle
Laboratoire d Enzymologie Moléculaire et Fonctionnelle, Département de Biologie, Institut Jacques Monod, UMR 7592, CNRS-Universités Paris 6 & 7, Tour 43, 2, place Jussieu, 75251 Paris Cedex 05, France.
J Soc Biol. 2004;198(3):263-78.
The maintenance of cellular homeostasis and the ability of cells to respond to their environment depend on the degradation of bulk proteins and orderly degradation of key regulatory proteins and their inhibitors. The 26S proteasome plays an essential role in these degradations. It is involved in the activation and inactivation of many cellular processes such as cell cycle progression, apoptosis and regulation of gene expression. It presents unique structural and functional properties. It degrades proteins by an unusual mechanism. Several series of proteasome inhibitors have been developed, useful to elucidate the biological roles of this multicatalytic enzyme. Velcade (bortezomid) was the first proteasome inhibitor to undergo, in may 2003, clinical trials in cancer patients.
细胞内环境稳定的维持以及细胞对其环境作出反应的能力取决于大量蛋白质的降解以及关键调节蛋白及其抑制剂的有序降解。26S蛋白酶体在这些降解过程中起着至关重要的作用。它参与许多细胞过程的激活和失活,如细胞周期进程、细胞凋亡和基因表达调控。它具有独特的结构和功能特性。它通过一种不同寻常的机制降解蛋白质。已经开发出了几类蛋白酶体抑制剂,有助于阐明这种多催化酶的生物学作用。万珂(硼替佐米)是2003年5月首个进入癌症患者临床试验的蛋白酶体抑制剂。