Notch信號通路

Notch signaling pathway

Notch 信號途徑：Notch信號傳導途徑在無脊椎動物和脊椎動物中廣泛存在且高度保守。此途徑介導由局部細胞間相互作用而產生的、對多種不成熟細胞分化的抑制信號，在胚胎發育中起重要作用。哺乳類動物中Notch途徑的功能復雜多樣，參與造血、T細胞發育、血管生成等重要生理過程，并與腫瘤形成和某些神經系統疾病有密切關系。

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.

一條重要的Notch信號途徑涉及Notch的三步蛋白質水解活化。許多相關分子 和體內生化過程參與Notch信號途徑調控。調控發生在不同水平,包括Notch-配體互作、受體和配體的運輸、泛素化降解等。

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