Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Cell Cycle. 2010 Oct 1;9(19):3904-12. doi: 10.4161/cc.9.19.13585. Epub 2010 Oct 11.
Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets various substrates for proteolysis inside and outside of the cell cycle. The activation of APC/C is dependent on two WD-40 domain proteins, Cdc20 and Cdh1. While APC/Cdc20 principally regulates mitotic progression, APC/Cdh1 shows a broad spectrum of substrates in and beyond cell cycle. In the past several years, numerous biochemical and mouse genetic studies have greatly attracted our attention to the emerging role of APC/Cdh1 in genomic integrity, cellular differentiation and human diseases. This review will aim to summarize the recently expanded understanding of APC/Cdh1 in regulating biological function and how its dysfunction may lead to diseases.
后期促进复合物/环体(APC/C)是一种多功能泛素蛋白连接酶,可针对细胞周期内外的各种底物进行蛋白水解。APC/C 的激活依赖于两个 WD-40 结构域蛋白,Cdc20 和 Cdh1。虽然 APC/Cdc20 主要调节有丝分裂进程,但 APC/Cdh1 在细胞周期内外显示出广泛的底物谱。在过去的几年中,大量的生化和小鼠遗传学研究极大地引起了我们对 APC/Cdh1 在基因组完整性、细胞分化和人类疾病中的新兴作用的关注。本综述旨在总结 APC/Cdh1 在调节生物功能方面的最新扩展认识,以及其功能障碍如何导致疾病。