Reactome | Signaling by NOTCH1 PEST Domain Mutants in Cancer

Signaling by NOTCH1 PEST Domain Mutants in Cancer

Stable Identifier

R-HSA-2644602

Type

Pathway

Species

Homo sapiens

Locations in the PathwayBrowser

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

Participants

Events

Constitutive Signaling by NOTCH1 PEST Domain Mutants (Homo sapiens)

Participant Of

hasEvent

Signaling by NOTCH1 in Cancer

Disease

Name	Identifier	Synonyms
cancer	162	malignant tumor, malignant neoplasm, primary cancer