p-NICD1 PEST domain mutants do not bind FBXW7

Stable Identifier
R-HSA-2220967
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
p-NICD1 PEST domain mutants do not bind FBXW7
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
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
PubMed ID Title Journal Year
17646408 The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia

Basso, G, Sulis, ML, Buonamici, S, Thompson, BJ, Aifantis, I, Palomero, T, Vilimas, T, Ferrando, AA

J Exp Med 2007
17646409 FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors

Draetta, G, Rao, S, Sears, R, Strack, P, Tibbitts, D, Hardwick, J, Pieters, R, Look, AT, Welcker, M, Meijerink, JP, Winter, C, Grim, J, O'Neil, J, Clurman, BE

J Exp Med 2007
Participants
Input
Participates
as an event of
Normal reaction
Phosphorylated NICD1 binds FBXW7 (Homo sapiens)
Functional status

Loss of function of p-NICD1 PEST domain mutants [nucleoplasm]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
T-cell acute lymphoblastic leukemia DOID:5603
Authored
Orlic-Milacic, M  (2013-01-04)
Reviewed
Haw, R  (2013-02-10)
Created
Orlic-Milacic, M  (2012-05-03)
Cite Us!