p-NICD1 PEST domain mutants do not bind FBXW7

Stable Identifier
R-HSA-2220967
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
17646409 FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors

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

J Exp Med 2007
17646408 The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia

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

J Exp Med 2007
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
T-cell leukemia 715
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created