NEXT1 PEST domain mutants are cleaved to produce NICD1 PEST domain mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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NEXT1 PEST domain mutant fragments are expected to be cleaved by the gamma-secretase complex at the S3 site in a similar manner to wild-type NEXT1 (Schroeter et al. 1998, De Strooper et al. 1999, Huppert et al. 2000, Fortini 2002, Rustighi et al. 2009).
Literature References
PubMed ID Title Journal Year
10879540 Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1

Saxena, MT, Huppert, SS, Kopan, R, Schroeter, EH, Milner, LA, Mumm, JS, Le, A

Nature 2000
19151708 The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer

Di Fiore, PP, Del Sal, G, Napoli, M, Rustighi, A, Rosato, A, Capobianco, A, Soldano, A, Nuciforo, P, Pece, S, Tiberi, L, Kaplan, F

Nat Cell Biol 2009
12209127 Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling

Fortini, ME

Nat Rev Mol Cell Biol 2002
9620803 Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain

Kopan, R, Kisslinger, JA, Schroeter, EH

Nature 1998
10206645 A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain

Wolfe, MS, Kopan, R, De Strooper, B, Schrijvers, V, Schroeter, EH, Cupers, P, Goate, A, Saftig, P, Craessaerts, K, Ray, WJ, Mumm, JS, Annaert, W

Nature 1999
Catalyst Activity

aspartic-type endopeptidase activity of gamma-secretase complex [plasma membrane]

Normal reaction
Functional status

Gain of function of NEXT1 PEST domain mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
T-cell acute lymphoblastic leukemia DOID:5603
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