Regulation of Delta And Notch

Regulation of Delta and Notch proteins occurs via specific E3 Ubiquitin ligases. The more ubiquitin added to the protein, the shorter it's half life. 

Su(dx)/Itch:

• E3 ubiquitin ligase complex accepts ubiquitin from an E2 conjugating enzyme, it transfers this ubiquitin to Notch proteins.
• This targets Notch for degradation acting as a mechanism of down-regulation of Notch.
• Su(dx) WW domain binds Notch, C2 domain localizes it to the membrane and HECT domain mediates ubiquitination.

Sel-10:

• Targets Notch(intra) i.e. the form of Notch after S3 cleavage found in the nucleus.
• Sel-10 recognises this phosphorylated form of Notch and recruits ubiquitin ligase activity via its F-Box domain to down regulate Notch(intra).  

Neur/Mib:

• Dmib in Drosophila.
• Mind bomb (Mib) protein acts on Delta ligand.
• It up-regulates Delta and promotes its endocytosis and degradation via its RING domain. 
• N-terminal domain interacts with Delta.
• Ubiquitination occurs in the intracellular domain of Delta.
• This activity acts to aid S3 cleavage whereby when Delta and Notch are bound, S2 cleavage occurs, Delta is then endocytosed pulling the extracellular portion of Notch receptor with it. By extracting this extracellular portion, S3 cleavage is helped along leaving Notch(intra) to translocate to the nucleus. 

(Image decpicts the ubiquitylation system. Image taken from: Wikipedia)