- References (2)
- Inventor Info
|Antigen/Gene or Protein Targets
|F-box/WD repeat–containing protein 7, CDC4, Sel10, Ago, Fbw7, SCF, Skp1/Cullin/F-box protein, E3 ubiquitin ligase complex,FBW6, FBX30, FBXO30, FBXW6, SEL-10, hAgo, hCdc4
Fbxw7 is a member of the F-box protein family, characterised by a motif of approximately 40 amino acids called the F-box. These proteins constitute one of the four subunits of ubiquitin protein ligase complex called SKP1-cullin-F-box and function in phosphorylation-dependent ubiquitination. Fbxw7 specifically protein contains 7 tandem solenoid protein domains also know as WD40 repeats. Fbwx7 binds directly to cyclin E and probably targets it for ubiquitin-mediated degradation.
There are 3 classes of F-box proteins:
Fbws containing WD-40 domains
Fbls containing leucine-rich repeats
Fbxs containing either different protein-protein interaction modules or no recognizable motifs
Mutations in Fbwx7 are known to be detected in several cancers, including ovarian, breast and colorectal cancer. Indications like these identify the Fbwx7 gene's potential role in the pathogenesis of human cancers.
|A targeting construct was engineered where exon 5 of the Fbxw7 gene was flanked with two LoxP sites and located near a pPGK -NeoR cassette flanked by two FRT sites. This fragment was subcloned into pDT vector and linearized before being electroporated into embryonic stem cells., selected and the Fbxw7 mouse was generated according to standard protocols.
|Requires expression of Cre recombinase to mediate excision of the lox P sites excising exon 5 of the Fbwx7 gene rendering it functionless
|Mouse Genetic Background/Cross History
|Back-crossed 5 times
|Cancer, Drug Discovery & Development, Metabolism
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