Notch signaling pathway

The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch proteins (Notch1-Notch4 in vertebrates) are single-pass receptors that are activated by the Delta (or Delta-like) and Jagged/Serrate families of membrane-bound ligands. They are transported to the plasma membrane as cleaved, but otherwise intact polypeptides. Interaction with ligand leads to two additional proteolytic cleavages that liberate the Notch intracellular domain (NICD) from the plasma membrane. The NICD translocates to the nucleus, where it forms a complex with the DNA binding protein CSL, displacing a histone deacetylase (HDAc)-co-repressor (CoR) complex from CSL. Components of an activation complex, such as MAML1 and histone acetyltransferases (HATs), are recruited to the NICD-CSL complex, leading to the transcriptional activation of Notch target genes.

棘层信号通路是一种在动物界所有多细胞生物胚胎发育中至关重要的进化保守性细胞间信号传导机制。棘层蛋白（在脊椎动物中为Notch1至Notch4）是一种单次跨膜受体，其被Delta（或Delta样）及Jagged/Serrate家族的膜结合配体激活。这些蛋白以切割但结构完整的多肽形式被转运至质膜。与配体的相互作用导致进一步的蛋白水解切割，从而将棘层蛋白的细胞内域（NICD）从质膜上释放出来。NICD随后转移至细胞核，在那里它与DNA结合蛋白CSL形成复合物，并将含有组蛋白脱乙酰化酶（HDAc）共抑制因子（CoR）的复合物从CSL上置换出去。激活复合物的组分，如MAML1和组蛋白乙酰转移酶（HATs），被招募至NICD-CSL复合物，进而导致棘层靶基因的转录激活。