Reactome: A Curated Pathway Database

Signaling by NOTCH1 PEST Domain Mutants in Cancer

Stable Identifier
R-HSA-2644602
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

NOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prolonged half-life of the intracellular NOTCH1 fragment, NICD1, and increased NICD1 transcriptional activity (Weng et al. 2004, Thompson et al. 2007, O'Neil et al. 2007).

Literature References
PubMed ID Title Journal Year
15472075 Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia Science 2004
17646409 FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors J Exp Med 2007
17646408 The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia J Exp Med 2007
Participants
events
Participant Of
hasEvent
Disease
Diseases
Name Identifier Synonyms
cancer 162 [malignant tumor, malignant neoplasm, primary cancer]
 
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