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

Stable Identifier
R-HSA-2220944
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
9244301 Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis

Pan, D, Rubin, GM

Cell 1997
12354787 The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts

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

Hum Mol Genet 2002
10882063 A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE

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

Mol Cell 2000
17401372 Structural basis for autoinhibition of Notch

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

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

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

J Biol Chem 2009
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
metallopeptidase activity of ADAM10/17:Zn2+ [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
T-cell leukemia 715
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created