Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
Curr Opin Cell Biol. 2018 Apr;51:103-109. doi: 10.1016/j.ceb.2017.12.008. Epub 2017 Dec 28.
The discovery that Notch activation involves a proteolytic cleavage to release the intracellular domain (NICD) revolutionized the field of Notch signaling. It resulted in a simple model whereby the cleaved NICD enters the nucleus and activates expression of genes by forming a DNA bound complex with CSL. However, is it really this simple? The realization that the outcome from activating Notch varies greatly from cell to cell raised many questions about what governs the target gene selections in different cell types. Insights have come from recent genome-wide studies, which highlight the importance of tissue-specific transcription factors and epigenetics. Co-factors also have been identified that participate in the regulation of enhancers. Finally, it is generally assumed that once cleaved, NICD goes on to do its job, but with a burgeoning number of post-translations, it may not be that simple.
Notch 激活涉及蛋白水解切割以释放细胞内结构域（NICD）的发现彻底改变了 Notch 信号转导领域。它形成了一个简单的模型，即被切割的 NICD 进入细胞核并通过与 CSL 形成 DNA 结合复合物来激活基因的表达。然而，真的这么简单吗？激活 Notch 产生的结果在细胞间差异很大，这引发了许多关于什么因素控制不同细胞类型中的靶基因选择的问题。最近的全基因组研究提供了一些见解，强调了组织特异性转录因子和表观遗传学的重要性。还确定了一些共同因子，它们参与增强子的调节。最后，人们普遍认为，一旦被切割，NICD 就会继续发挥作用，但随着越来越多的翻译后修饰，情况可能并非如此简单。
