Reactome: A Curated Pathway Database

Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer (R-HSA-2894858)

Species Homo sapiens

Summation

Mutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increase in NOTCH1 transcriptional activity and PEST domain mutations alone result in up to ~2-fold increase in NOTCH1 transcriptional activity, in cis mutations of HD and PEST domains act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold (Weng et al. 2004).

Locations in the PathwayBrowser
Diseases
Name Identifier Synonyms
T-cell leukemia 715
cancer 162 [malignant tumor, malignant neoplasm, primary cancer]
Literature References
pubMedId Title Journal Year
15472075 Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia Science 2004