Notch信号通路图(5张)

Notch signaling pathway



Notch 信号途径：Notch信号传导途径在无脊椎动物和脊椎动物中广泛存在且高度保守。此途径介导由局部细胞间相互作用而产生的、对多种不成熟细胞分化的抑制信号，在胚胎发育中起重要作用。哺乳类动物中Notch途径的功能复杂多样，参与造血、T细胞发育、血管生成等重要生理过程，并与肿瘤形成和某些神经系统疾病有密切关系。



Notch signaling pathway：Notch proteins are synthesized as precursor proteins that are processed by a furin-like convertase in the Golgi before being transported to the Cell surface, where they reside as heterodimers. Interaction of Notch receptors with their ligands, such as Delta-like or Jagged, leads to a cascade of proteolytic cleavages. The first cleavage is mediated by TACE (tumour-necrosis factor-α-convering enzyme/metalloproteinase), followed by a second cleavage mediated by the γ-secretase activity of presenilins (PS), which liberates the cytoplasmic domain —Notch intracellular domain (NIC) — of the Notch receptors. The liberated NIC enters the nucleus and binds to the transcription factor CSL, which displaces co-repressors (CoR) and recruits co-activators (CoA), leading to transcriptional activation of downstream target genes. This pathway is known as the CSL-dependent pathway. Genetic evidence points to the existence of a CSL-independent pathway that is poorly characterized at present.



一条重要的Notch信号途径涉及Notch的三步蛋白质水解活化。许多相关分子 和体内生化过程参与Notch信号途径调控。调控发生在不同水平,包括Notch-配体互作、受体和配体的运输、泛素化降解等。



在白血病转化中Notch潜在的信号通路