Ubiquitination of NICD1 by FBWX7

Stable Identifier
Reaction [transition]
Homo sapiens
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Once bound to FBXW7, phosphorylated NICD1 is ubiquitinated, which leads to degradation of NICD1 and downregulation of NOTCH1 signaling. FBXW7-mediated ubiquitination and degradation of NOTCH1 depend on the C-terminally located PEST domain of NOTCH1 (Fryer et al. 2004, Oberg et al. 2001, Wu et al. 2001). The PEST domain in NOTCH1 and the substrate binding WD40 domain in FBXW7 are frequent targets of mutations in T-cell acute lymphoblastic leukemia - T-ALL (Welcker and Clurman 2008).

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
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
18094723 FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation

Clurman, BE, Welcker, M

Nat Rev Cancer 2008
Catalyst Activity

ubiquitin-protein transferase activity of p-NICD1:FBXW7:SKP1:CUL1:RBX1 [nucleoplasm]

Inferred From
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