Kuhlmann Nathan J, Chien Peter
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, United States.
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, United States; Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, United States.
Curr Opin Microbiol. 2017 Apr;36:118-127. doi: 10.1016/j.mib.2017.03.013. Epub 2017 Apr 28.
Energy dependent proteolysis is essential for all life, but uncontrolled degradation leads to devastating consequences. In bacteria, oligomeric AAA+ proteases are responsible for controlling protein destruction and are regulated in part by adaptor proteins. Adaptors are regulatory factors that shape protease substrate choice by either restricting or enhancing substrate recognition in several ways. In some cases, protease activity or assembly itself requires adaptor binding. Adaptors can also alter specificity by acting as scaffolds to tether particular substrates to already active proteases. Finally, hierarchical assembly of adaptors can use combinations of several activities to enhance the protease's selectivity. Because the lifetime of the constituent proteins directly affects the duration of a particular signaling pathway, regulated proteolysis impacts almost all cellular responses. In this review, we describe recent progress in regulated protein degradation, focusing on fundamental principles of adaptors and how they perform critical biological functions, such as promoting cell cycle progression and quality control.
能量依赖型蛋白水解对所有生命至关重要,但不受控制的降解会导致毁灭性后果。在细菌中,寡聚AAA+蛋白酶负责控制蛋白质的降解,并且部分受衔接蛋白调控。衔接蛋白是通过多种方式限制或增强底物识别来塑造蛋白酶底物选择的调节因子。在某些情况下,蛋白酶活性或组装本身需要衔接蛋白结合。衔接蛋白还可以通过作为支架将特定底物拴系到已激活的蛋白酶上,从而改变特异性。最后,衔接蛋白的分级组装可以利用多种活性的组合来增强蛋白酶的选择性。由于组成蛋白的寿命直接影响特定信号通路的持续时间,因此受调控的蛋白水解几乎影响所有细胞反应。在本综述中,我们描述了受调控的蛋白质降解的最新进展,重点关注衔接蛋白的基本原理以及它们如何执行关键的生物学功能,例如促进细胞周期进程和质量控制。