School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.
Biomolecules. 2022 Jan 27;12(2):224. doi: 10.3390/biom12020224.
Notch is a developmental receptor, conserved in the evolution of the metazoa, which regulates cell fate proliferation and survival in numerous developmental contexts, and also regulates tissue renewal and repair in adult organisms. Notch is activated by proteolytic removal of its extracellular domain and the subsequent release of its intracellular domain, which then acts in the nucleus as part of a transcription factor complex. Numerous regulatory mechanisms exist to tune the amplitude, duration and spatial patterning of this core signalling mechanism. In , Deltex (Dx) and Suppressor of dx (Su(dx)) are E3 ubiquitin ligases which interact with the Notch intracellular domain to regulate its endocytic trafficking, with impacts on both ligand-dependent and ligand-independent signal activation. Homologues of Dx and Su(dx) have been shown to also interact with one or more of the four mammalian Notch proteins and other target substrates. Studies have shown similarities, specialisations and diversifications of the roles of these Notch regulators. This review collates together current research on vertebrate Dx and Su(dx)-related proteins, provides an overview of their various roles, and discusses their contributions to cell fate regulation and disease.
Notch 是一种发育性受体，在后生动物的进化中保守，它在许多发育环境中调节细胞命运的增殖和存活，也调节成年生物组织的更新和修复。Notch 通过其细胞外结构域的蛋白水解去除和随后其细胞内结构域的释放而被激活，然后作为转录因子复合物的一部分在核内发挥作用。存在许多调节机制来调节这种核心信号机制的幅度、持续时间和空间模式。在 中，Deltex (Dx) 和 Suppressor of dx (Su(dx)) 是 E3 泛素连接酶，与 Notch 细胞内结构域相互作用以调节其内吞运输，对配体依赖性和配体非依赖性信号激活都有影响。已经表明 Dx 和 Su(dx) 的同源物也与一种或多种四种哺乳动物 Notch 蛋白和其他靶标底物相互作用。研究表明这些 Notch 调节剂的作用具有相似性、专业化和多样化。这篇综述汇集了脊椎动物 Dx 和 Su(dx) 相关蛋白的当前研究，概述了它们的各种作用，并讨论了它们对细胞命运调节和疾病的贡献。
