Palermo R, Checquolo S, Bellavia D, Talora C, Screpanti I
Dipartimento di Medicina Molecolare, Sapienza Universita' di Roma, Viale Regina Elena 291, 00161 Roma, Italy.
Curr Mol Med. 2014 Jan;14(1):34-44. doi: 10.2174/1566524013666131118105216.
The Notch receptors have attracted considerable attention for their ability to control cellular functions that regulate embryo development and tissue homeostasis. Notch receptors act by controlling the expression of a specific set of target genes. If Notch signaling system can be so simple, and yet so complex in its pleiotropic effects, then a sophisticated network of regulatory mechanisms is required to maintain the control over the initiation, activity and termination of this signaling pathway. A multitude of regulatory mechanisms has been discovered that controls the interaction of Notch receptors with their ligands, the assembling of a Notch transcriptional activation complex and the termination of Notch signals. The intracellular and extracellular domains of the Notch receptors are synthesized as single proteins, pairing with each other during their trafficking through the exocytotic route. The mechanisms operating in the phase preceding the generation of the heterodimeric signal-competent Notch receptors can be as elaborate and physiologically important as those operating downstream of Notch receptor activation. These regulatory mechanisms, which are essential to understand the role of Notch signaling in human physiology and pathology are reviewed here.
Notch受体因其控制调节胚胎发育和组织稳态的细胞功能的能力而备受关注。Notch受体通过控制一组特定靶基因的表达来发挥作用。如果Notch信号系统可以如此简单，但其多效性效应却又如此复杂，那么就需要一个复杂的调节机制网络来维持对该信号通路的起始、活性和终止的控制。已经发现了多种调节机制，它们控制Notch受体与其配体的相互作用、Notch转录激活复合物的组装以及Notch信号的终止。Notch受体的细胞内和细胞外结构域作为单一蛋白质合成，在通过胞吐途径运输过程中相互配对。在产生具有信号能力的异二聚体Notch受体之前的阶段所起作用的机制，可能与Notch受体激活下游所起作用的机制一样精细且具有生理重要性。本文将对这些调节机制进行综述，这些机制对于理解Notch信号在人类生理学和病理学中的作用至关重要。
