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).