FBXW7 Mutants and NOTCH1 in Cancer

Stable Identifier
Homo sapiens
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FBXW7 (FBW7) is a component of the SCF (SKP1, CUL1, and F-box protein) ubiquitin ligase complex SCF-FBW7 which is involved in the degradation of NOTCH1 (Oberg et al. 2001, Wu et al. 2001, Fryer et al. 2004). Loss of function mutations in FBXW7 are frequently found in T-cell acute lymphoblastic leukemia (Akhoondi et al. 2007, Thompson et al. 2007, O'Neil et al. 2007) and are mutually exclusive with NOTCH1 PEST domain mutations (Thompson et al. 2007, O'Neil et al. 2007).
Literature References
PubMed ID Title Journal Year
11461910 The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog

Lendahl, U, Li, J, Wolf, E, Pauley, A, Oberg, C, Gurney, M

J Biol Chem 2001
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
11585921 SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation

Das, I, Wu, G, Deshaies, RJ, Kitajewski, J, Li, J, Pauley, A, Chui, I, Gurney, M, Lyapina, S

Mol Cell Biol 2001
15546612 Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover

Fryer, CJ, Jones, KA, White, JB

Mol Cell 2004
17909001 FBXW7/hCDC4 is a general tumor suppressor in human cancer

Grander, D, Dofou, D, Cepeda, D, von der Lehr, N, Fiegl, H, Marth, C, Hansson, J, Mueller-Holzner, E, Dagnell, M, Sun, D, Sangfelt, O, Corcoran, M, Akhoondi, S, Reed, SI, Apostolidou, S, Maljukova, A, Nordgren, H, Nejad, SZ, Spruck, C, Sangfelt, P, Egyhazi, S, Dafou, D, Klotz, K, Zali, MR, Nayer, BN, Widschwendter, M, Petersson, F

Cancer Res. 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
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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