DELTA NOTCH SIGNALLING PATHWAY

The Delta-Notch signalling pathway is a highly conserved cellular signaling 

mechanism that is essential for embryonic development .

Notch genes encode for transmembrane protiens, Delta is an example
 of one of the ligands that bind to the extracellular domain of the
 Notch receptor in Drosophila. Delta is a single-pass transmembrane
 protein ligand that is membrane bound. 

Notch signalling determines cell fate of surounding cells by the process of

 lateral inhibition in both vertbrates and invertebrates. 

Different Notch activation results in different biological alterations in

 gene expression. For example in human adult tissue, activation of Notch1 

corresponds to differentiation of T-cells and self-renewal, which path is 

undertaken is dependent on other environmental factors too.

• It involves proteolytic cleavage to release an intracellular fragment (Nicd) that functions to regulate transcription.
• In the nucleus, Nicd displaces a repression complex and, with the DNA-binding CSL (CBF1, Su(H) and LAG-1) protein, recruits . Additional epigenetic cofactors are implicated and recruitment of kinases and ubiquitin ligases probably contribute to rapid turnover of the activator complex.
• Activity of the receptor is also regulated post-translationally. A number of different auxiliary components are implicated, including several ubiquitin ligases and proteins, such as Numb, that have direct links to the endocytic machinery.
• 

  Notch ligands are transmembrane proteins and they require E3 ubiquitin ligases for their activity. The mechanisms whereby the ligands become competent to signal are not yet known, but probably entail endocytosis. Localization and cleavage of ligands might also contribute to their regulation.

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