Reactome: A Curated Pathway Database

NEXT1 is cleaved to produce NICD1 (R-HSA-157353) [Homo sapiens]


NEXT1 fragment of NOTCH1 is further cleaved at S3 by the presenilin-1 (PSEN1) containing gamma-secretase complex, which releases the intracellular domain NICD1 into the cytosol (Schroeter et al. 1998, De Strooper et al. 1999, Huppert et al. 2000, Fortini et al. 2002). PIN1, a prolyl isomerase, was recently found to bind phosphorylated Ser/Thr-Pro motifs in the cytoplasmic domain of NOTCH1 and potentiate NEXT1 cleavage by gamma-secretase. This generates a positive loop in NOTCH1 signaling since PIN1 is a transcriptional target of NICD1 (Rustighi et al. 2009).

Additional Information
Compartment cytosol , plasma membrane
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Input entries
Output entries
Catalyst Activity
PhysicalEntity Activity Active Units
gamma-secretase complex aspartic-type endopeptidase activity (0004190)