Poellinger Lorenz, Lendahl Urban
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, von Eulers väg 3, SE-171 77 Stockholm, Sweden.
Curr Opin Genet Dev. 2008 Oct;18(5):449-54. doi: 10.1016/j.gde.2008.07.013. Epub 2008 Sep 4.
Despite a relatively simple core-signaling transduction machinery, Notch signaling controls cell differentiation in many different tissues and at multiple stages in a given cell lineage. To understand how Notch generates this multitude of cellular responses, it is important to learn how the Notch-signaling output is modulated at various levels. Pathway-intrinsic as well as pathway-extrinsic mechanisms, including cross-talk between Notch and other major signaling mechanisms, modulate Notch signaling, contributing to the versatile output. In this review, we discuss how Notch signaling is altered in tumors and illustrate the complexity in signaling pathway cross-talk with examples of how Notch synergizes with NF-kappaB signaling and the cellular response to lowered oxygen (hypoxia).
尽管Notch信号传导的核心机制相对简单，但它在许多不同组织以及特定细胞谱系的多个阶段控制细胞分化。为了理解Notch如何产生如此众多的细胞反应，了解Notch信号输出在各个水平上是如何被调节的很重要。包括Notch与其他主要信号机制之间的相互作用在内的信号通路内在和外在机制，调节Notch信号传导，促成了其多样的输出。在这篇综述中，我们讨论了Notch信号在肿瘤中是如何改变的，并通过Notch与NF-κB信号协同作用以及细胞对低氧（缺氧）反应的例子来说明信号通路相互作用的复杂性。
