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Pathway Description
Notch signaling
Homo sapiens
Category:
Protein Pathway
Sub-Categories:
Created: 2025-02-06
Last Updated: 2025-04-08
The Notch signaling pathway involves a series of interactions and processes that regulate cell differentiation and development. The pathway is initiated when Fringe and delta-like canonical Notch ligand 3 interact with Notch receptor 1, leading to the activation of the receptor. Additionally, Pre-Notch, an immature form of the receptor, is processed and activated by Fringe, which ultimately leads to the formation of active Notch receptor 1. The Gamma-secretase complex, consisting of APH1B, PSEN1, PSENEN, and NCSTN, is crucial for the activation of Notch receptor 1, triggering downstream signaling. Once activated, Notch receptor 1 binds to Neurogenic locus notch homolog protein 1 (Notch1), which then activates Recombining binding protein suppressor of hairless-like protein (RBPJ-like), a key transcriptional regulator in the pathway. Furthermore, several inhibitors, such as Segment polarity protein dishevelled homolog DVL-1 (DVL1), Protein numb homolog, and E3 ubiquitin-protein ligase Itchy homolog, suppress Notch receptor 1 activity to fine-tune the signaling response. MAML (Mastermind-like protein) and Histone acetyltransferases (HATs) enhance the transcriptional activity of RBPJ-like, further activating genes that are essential for Notch signaling. In terms of transport, Notch1 is shuttled from the cytosol to the nucleus, where it exerts its transcriptional effects. Meanwhile, Pre-Notch is transported from the Endoplasmic Reticulum membrane to the Golgi apparatus for further maturation before becoming functional Notch receptor 1.
References
Notch signaling References
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