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NCSTN — NOTCH1

Pathways - manually collected, often from reviews:

• KEGG Notch signaling pathway: Complex of APH1A-NCSTN-PSEN1-PSEN2-PSENEN → NOTCH1/NOTCH2/NOTCH3/NOTCH4 (protein-protein, activation)
  
• NCI Pathway Database Notch signaling pathway: NOTCH1 heterodimer/DNER complex (NOTCH1-DNER) → Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) (modification, collaborate)
  De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Fraering et al., Biochemistry 2004, Eiraku et al., Nat Neurosci 2005, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) → NICD (NOTCH1) (modification, activates) De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Fraering et al., Biochemistry 2004, Eiraku et al., Nat Neurosci 2005, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: NOTCH1 heterodimer/NB-3 complex (NOTCH1-CNTN6) → Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) (modification, collaborate)
  De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Cui et al., J Biol Chem 2004, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) → NICD (NOTCH1) (modification, activates) De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Cui et al., J Biol Chem 2004, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Presenilin action in Notch and Wnt signaling: NEXT (NOTCH1) → Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) (modification, collaborate)
  Mumm et al., Mol Cell 2000
  Evidence: assay, other species
• NCI Pathway Database Presenilin action in Notch and Wnt signaling: Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) → NICD (NOTCH1) (modification, activates) Mumm et al., Mol Cell 2000
  Evidence: assay, other species
• NCI Pathway Database Notch signaling pathway: NOTCH1 heterodimer/CNTN1 complex (NOTCH1-CNTN1) → Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) (modification, collaborate)
  De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Hu et al., Cell 2003, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) → NICD (NOTCH1) (modification, activates) De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Hu et al., Cell 2003, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: NEXT (NOTCH1) → Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) (modification, collaborate)
  De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Notch signaling pathway: Gamma Secretase complex (PSEN1-NCSTN-APH1A-PSENEN-APH1B) → NICD (NOTCH1) (modification, activates) De Strooper et al., Nature 1999, Ray et al., J Biol Chem 1999, Mumm et al., Mol Cell 2000, Mizutani et al., Proc Natl Acad Sci U S A 2001, Saxena et al., J Biol Chem 2001, Lee et al., J Biol Chem 2002, Schroeter et al., Proc Natl Acad Sci U S A 2003, Fraering et al., Biochemistry 2004, Kopan et al., Proc Natl Acad Sci U S A 1996, Schroeter et al., Nature 1998
  Evidence: mutant phenotype, assay, physical interaction
• Reactome Reaction: NOTCH1 → NCSTN (reaction) De Strooper et al., Nature 1999, Huppert et al., Nature 2000*, Fortini et al., Nat Rev Mol Cell Biol 2002, Rustighi et al., Nat Cell Biol 2009*, Schroeter et al., Nature 1998
• WikiPathways Notch Signaling Pathway: APH1A/APH1B/TNF/PSEN1/PSEN2/NCSTN → NOTCH2/NOTCH3/NOTCH4/NOTCH1 (activation)
  

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Bind_translation Interaction: NCSTN — NOTCH1 (coimmunoprecipitation) Shah et al., Cell 2005*
• IRef Bind_translation Interaction: NCSTN — NOTCH1 (affinity chromatography technology) Shah et al., Cell 2005*

Text-mined interactions from Literome

Mumm et al., Mol Cell 2000 : Gamma-secretase-like proteolysis at site 3 ( S3 ), within the transmembrane domain, releases the Notch intracellular domain ( NICD ) and activates CSL mediated Notch signaling
López-Schier et al., Dev Cell 2002 : Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step
Li et al., J Biol Chem 2003 : These data demonstrate that Nicastrin is essential for the gamma-secretase cleavage of APP and Notch in mammalian cells and that Nicastrin has both positive and negative functions in the regulation of gamma-secretase activity
Curry et al., Oncogene 2005 (Sarcoma, Kaposi) : Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi 's sarcoma tumor cells
Koyanagi et al., Circ Res 2007 : Gamma-secretase dependent Notch activation is required for cardiac gene expression in human cells and induces the expression of noncanonical Wnt proteins, which may act in a paracrine manner to further amplify cardiac differentiation
Real et al., Nat Med 2009 (Precursor T-Cell Lymphoblastic Leukemia-Lymphoma) : Gamma-secretase inhibitors (GSIs) block the activation of the oncogenic protein Notch homolog-1 (NOTCH1) in T cell acute lymphoblastic leukemia ( T-ALL )
Pui et al., Cancer Cell 2009 (Precursor T-Cell Lymphoblastic Leukemia-Lymphoma) : Gamma-secretase inhibitors block the activation of NOTCH1 but have limited activity against T cell acute lymphoblastic leukemia ( T-ALL ) and cause severe gastrointestinal toxicity
Shimoyama et al., Arterioscler Thromb Vasc Biol 2010 (Diabetes Mellitus, Experimental...) : Gamma secretase inhibitor, an inhibitor of Notch signaling, partially inhibited the enhanced expression of p21 induced by CCN3
Li et al., Neurol Sci 2012 (Brain Ischemia) : Gamma-secretase inhibitor, N- [ N- ( 3,5-difluorophenacetyl ) -1-alanyl ] -S-phenylglycine t-butyl ester ( DAPT ) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-?B pathway that contributes to the brain damage after stroke