NOTCH1 HD+PEST domain mutants are cleaved by ADAM10/17 irrespective of ligand binding

Stable Identifier
R-HSA-2220976
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

NOTCH1 HD domain mutants are cleaved at S2 and S3 sites to produce NEXT1 and NICD1 fragments, respectively, in the absence of DLL/JAG ligand binding, although they are responsive to DLL/JAG ligands. NOTCH1 mutants containing in cis mutations in the HD and PEST domains are expected to be constitutively cleaved at the S2 site by ADAM10/17, like NOTCH1 HD domain mutants (Malecki et al. 2006), resulting in release of NEXT1 PEST domain mutant fragments.

Literature References
PubMed ID Title Journal Year
16738328 Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes

Malecki, MJ, Sanchez-Irizarry, C, Mitchell, JL, Histen, G, Xu, ML, Aster, JC, Blacklow, SC

Mol. Cell. Biol. 2006
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
metallopeptidase activity of ADAM10/17:Zn2+ [plasma membrane]
Physical Entity
Activity
Disease
Name Identifier Synonyms
T-cell leukemia 715
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created