ADAM10/17 cleaves ligand-bound NOTCH1 PEST domain mutants to produce NEXT1 PEST domain mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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After NOTCH1 PEST domain mutants bind a DLL (DLL1 or DLL4) or JAG ligand (JAG1 or JAG2) in trans, they are expected to be cleaved by ADAM10 or ADAM17 metalloproteases, like the wild-type ligand-bound NOTCH1, to produce NEXT1 PEST domain mutant fragments (Pan and Rubin 1997, Brou et al. 2000, Hartmann et al. 2002, Gordon et al. 2007, van Tetering et al. 2009).

Literature References
PubMed ID Title Journal Year
12354787 The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts

Hartmann, D, De Strooper, B, Herreman, A, Lena Illert, A, Saftig, P, L├╝bke, T, von Figura, K, Craessaerts, K, Umans, L, Annaert, W, Serneels, L

Hum Mol Genet 2002
9244301 Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis

Pan, D, Rubin, GM

Cell 1997
10882063 A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE

Bessia, C, Black, RA, Roux, P, LeBail, O, Doedens, JR, Gupta, N, Brou, C, Israel, A, Logeat, F, Cumano, A

Mol Cell 2000
17401372 Structural basis for autoinhibition of Notch

Blacklow, SC, Vardar-Ulu, D, Sanchez-Irizarry, C, Aster, JC, Gordon, WR, Histen, G

Nat Struct Mol Biol 2007
19726682 Metalloprotease ADAM10 is required for Notch1 site 2 cleavage

Kopan, R, Verlaan, I, van Tetering, G, van der Wall, E, Vooijs, M, van Diest, P

J Biol Chem 2009
Catalyst Activity

metallopeptidase activity of ADAM10/17:Zn2+ [plasma membrane]

Normal reaction
Functional status

Gain of function of Ub-DLL/JAG:NOTCH1 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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