Schmidt Marion, Hanna John, Elsasser Suzanne, Finley Daniel
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA.
Biol Chem. 2005 Aug;386(8):725-37. doi: 10.1515/BC.2005.085.
The proteasome is a compartmentalized, ATP-dependent protease composed of more than 30 subunits that recognizes and degrades polyubiquitinated substrates. Despite its physiological importance, many aspects of the proteasome's structural organization and regulation remain poorly understood. In addition to the proteins that form the proteasome holocomplex, there is increasing evidence that proteasomal function is affected by a wide variety of associating proteins. A group of ubiquitin-binding proteins assist in delivery of substrates to the proteasome, whereas proteasome-associated ubiquitin ligases and deubiquitinating enzymes may alter the dynamics of ubiquitin chains already associated with the proteasome. Some proteins appear to influence the overall stability of the complex, and still others have the capacity to activate or inhibit the hydrolytic activity of the core particle. The increasing number of interacting proteins identified suggests that proteasomes, as they exist in the cell, are larger and more diverse in composition than previously assumed. Thus, the study of proteasome-associated proteins will lead to new perspectives on the dynamics of this uniquely complex proteolytic machine.
蛋白酶体是一种分隔的、依赖ATP的蛋白酶，由30多个亚基组成，可识别并降解多聚泛素化底物。尽管其在生理上具有重要性，但蛋白酶体的结构组织和调节的许多方面仍知之甚少。除了形成蛋白酶体全复合物的蛋白质外，越来越多的证据表明，蛋白酶体的功能受到多种相关蛋白的影响。一组泛素结合蛋白协助将底物递送至蛋白酶体，而蛋白酶体相关的泛素连接酶和去泛素化酶可能会改变已经与蛋白酶体相关的泛素链的动态变化。一些蛋白质似乎会影响复合物的整体稳定性，还有一些蛋白质能够激活或抑制核心颗粒的水解活性。已鉴定出的相互作用蛋白数量不断增加，这表明细胞中的蛋白酶体在组成上比以前认为的更大且更多样化。因此，对蛋白酶体相关蛋白的研究将为这一独特复杂的蛋白水解机器的动态变化带来新的视角。
