Hochstrasser M
Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, USA.
Annu Rev Genet. 1996;30:405-39. doi: 10.1146/annurev.genet.30.1.405.
A growing number of cellular regulatory mechanisms are being linked to protein modification by the polypeptide ubiquitin. These include key transitions in the cell cycle, class I antigen processing, signal transduction pathways, and receptor-mediated endocytosis. In most, but not all, of these examples, ubiquitination of a protein leads to its degradation by the 26S proteasome. Following attachment of ubiquitin to a substrate and binding of the ubiquitinated protein to the proteasome, the bound substrate must be unfolded (and eventually deubiquitinated) and translocated through a narrow set of channels that leads to the proteasome interior, where the polypeptide is cleaved into short peptides. Protein ubiquitination and deubiquitination are both mediated by large enzyme families, and the proteasome itself comprises a family of related but functionally distinct particles. This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves.
越来越多的细胞调节机制与多肽泛素介导的蛋白质修饰相关联。这些机制包括细胞周期中的关键转变、I类抗原加工、信号转导途径以及受体介导的内吞作用。在大多数（但并非所有）这些例子中，蛋白质的泛素化会导致其被26S蛋白酶体降解。在泛素附着到底物以及泛素化蛋白质与蛋白酶体结合之后，结合的底物必须被展开（最终去泛素化）并通过一组狭窄的通道转运到蛋白酶体内部，在那里多肽被切割成短肽。蛋白质泛素化和去泛素化均由大型酶家族介导，并且蛋白酶体本身由一组相关但功能不同的颗粒组成。这种多样性是泛素系统高底物特异性及其所服务的多种调节机制的基础。
