Disease relevance of Fbxw7

• Although p53-deficient mice primarily develop lymphomas and sarcomas, the additional loss of one copy of the Fbxw7 gene drives tumor development in a range of epithelial tissues [1].

High impact information on Fbxw7

• We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1 [2].
• We have recently identified Fbxw7/Cdc4 as a downstream target of p53 loss that controls genomic instability and tumor development in epithelial tumors [1].
• Control of genomic instability and epithelial tumor development by the p53-Fbxw7/Cdc4 pathway [1].
• Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7(-/-) embryos [3].
• Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development [3].

Biological context of Fbxw7

• Three isoforms (alpha, beta, and gamma) of Fbxw7 are produced from mRNAs with distinct 5' exons [4].

Regulatory relationships of Fbxw7

• Our results thus indicate that expression of Fbxw7 isoforms is differentially regulated in a cell cycle- or p53-dependent manner [4].

References