Reactome: A Curated Pathway Database

p-NICD1 PEST domain mutants do not bind FBXW7

Stable Identifier
R-HSA-2220967
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

As binding of WD40 repeats of FBXW7 requires conserved phosphodegron in the PEST domain of NICD1, especially phosphorylation of threonine residue T2511 and serine residue S2513, FBXW7 cannot bind NICD1 PEST domain mutants which lack the conserved phosphodegron due to truncation of the PEST domain, or are not phosphorylated on conserved threonine and serine residues due to point mutations. Inability to bind FBXW7 and undergo FBXW7-mediated ubiquitination and degradation prolongs the half-life of NICD1 PEST domain mutants and results in persistent NOTCH1 signaling (O'Neil et al. 2007, Thompson et al. 2007).

Literature References
Participants
Participant Of
Disease
Diseases
Name Identifier Synonyms
T-cell leukemia 715
cancer 162 [malignant tumor, malignant neoplasm, primary cancer]