Notch is synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase (S1 cleavage) in the trans-golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved (S2 cleavage) by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin-dependent gamma-secretase (S3 cleavage) to release the intracellular domain (NICD) from the membrane which then translocates to the nucleus to activate transcription of downstream genes.
Notch1 - A multifunctional transmembrane receptor Notch1 is a member of the Notch family of Type 1 single-pass transmembrane proteins that share an extracellular domain of multiple epidermal growth factor-like (EGF) repeats. Notch family members play key roles in a variety of developmental process... Read more.