Kovall Rhett A, Gebelein Brian, Sprinzak David, Kopan Raphael
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Dev Cell. 2017 May 8;41(3):228-241. doi: 10.1016/j.devcel.2017.04.001.
The Notch signaling pathway relies on a proteolytic cascade to release its transcriptionally active intracellular domain, on force to unfold a protective domain and permit proteolysis, on extracellular domain glycosylation to tune the forces exerted by endocytosed ligands, and on a motley crew of nuclear proteins, chromatin modifiers, ubiquitin ligases, and a few kinases to regulate activity and half-life. Herein we provide a review of recent molecular insights into how Notch signals are triggered and how cell shape affects these events, and we use the new insights to illuminate a few perplexing observations.
Notch信号通路依赖于蛋白水解级联反应来释放其具有转录活性的细胞内结构域,依赖于作用力来展开一个保护结构域并允许蛋白水解,依赖于细胞外结构域糖基化来调节内吞配体施加的作用力,还依赖于一群形形色色的核蛋白、染色质修饰因子、泛素连接酶以及一些激酶来调节活性和半衰期。在此,我们综述了关于Notch信号如何被触发以及细胞形状如何影响这些事件的最新分子见解,并利用这些新见解来阐明一些令人困惑的观察结果。