Landor Sebastian K-J, Lendahl Urban
Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Department of Cell Biology, Åbo Akademi University, FI-20520 Turku, Finland.
Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Department of Cell Biology, Åbo Akademi University, FI-20520 Turku, Finland.
Exp Cell Res. 2017 Jul 15;356(2):146-151. doi: 10.1016/j.yexcr.2017.04.030. Epub 2017 Apr 26.
The ability to sense and adapt to low oxygen levels (hypoxia) is central for most organisms and cell types. At the center of this process is a molecular mechanism, the cellular hypoxic response, in which the hypoxia inducible factors (HIFs) are stabilized by hypoxia, allowing the HIF proteins to act as master transcriptional regulators to adjust the cell to a low oxygen environment. In recent years, it has become increasingly appreciated that the cellular hypoxic response does not always operate in splendid isolation, but intersects with signaling mechanisms such as Notch signaling, a key regulatory signaling mechanism operating in most cell types controlling stem cell maintenance and differentiation. In this review, which is dedicated to the memory of Lorenz Poellinger, we discuss how the intersection between Notch and the cellular hypoxic response was discovered and our current understanding of the molecular basis for the cross-talk. We also provide examples of where Notch and hypoxia intersect in various physiological and disease contexts.
感知并适应低氧水平（缺氧）的能力对大多数生物体和细胞类型来说至关重要。这一过程的核心是一种分子机制，即细胞缺氧反应，其中缺氧诱导因子（HIFs）在缺氧状态下被稳定下来，使HIF蛋白能够作为主要的转录调节因子，将细胞调整到低氧环境。近年来，人们越来越认识到细胞缺氧反应并不总是孤立运行，而是与诸如Notch信号传导等信号机制相互交叉，Notch信号传导是大多数细胞类型中控制干细胞维持和分化的关键调节信号机制。在这篇纪念洛伦兹·珀林格的综述中，我们讨论了Notch与细胞缺氧反应之间的交叉是如何被发现的，以及我们目前对这种相互作用分子基础的理解。我们还提供了Notch与缺氧在各种生理和疾病背景下相互交叉的例子。
