Phosphorylated NICD1 binds FBXW7

Stable Identifier
Reaction [binding]
Homo sapiens
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The E3 ubiquitin ligase FBXW7, a homologue of C. elegans sel-10, binds phosphorylated NOTCH1 intracellular domain, p-NICD1 (Oberg et al. 2001, Fryer et al. 2004, Wu et al. 2001). FBXW7 is a substrate recognition component of an E3 ubiquitin-protein ligase complex that also contains SKP1, CUL1 and RBX1. FBXW7 has three transcriptional isoforms, known as FBXW7 alpha, FBXW7 beta and FBXWT gamma. While FBXW7 beta is cytosolic, FBXW7 alpha and gamma are nuclear, with FBXW7 gamma localizing to the nucleolus. FBXW7 alpha is the most abundant isoform and the one directly shown to interact with NICD1 (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
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