NEXT1 is cleaved to produce NICD1 Authored: Jassal, B, 2004-12-15 13:08:03 EC Number: 3.4.23 Edited: D'Eustachio, P, 2012-02-06 Edited: Orlic-Milacic, M, 2012-02-10 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). Pubmed10206645 Pubmed10879540 Pubmed12209127 Pubmed19151708 Pubmed9620803 Reactome Database ID Release 43157353 Reactome, http://www.reactome.org ReactomeREACT_1784 Reviewed: Haw, R, 2012-02-06 Reviewed: Joutel, A, 2004-12-15