Signaling by NOTCH1 PEST Domain Mutants in Cancer

Stable Identifier
R-HSA-2644602
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Signaling by NOTCH1 PEST Domain Mutants in Cancer
Click the image above or here to open this pathway in the Pathway Browser
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

Lee, W, Blacklow, SC, Silverman, LB, Look, AT, Sanchez-Irizarry, C, Aster, JC, Ferrando, AA, Weng, AP, Morris JP, 4th

Science 2004
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
Events
Participates
as an event of
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2013-01-04)
Reviewed
Haw, R  (2013-02-10)
Created
Orlic-Milacic, M  (2012-11-22)
Cite Us!