ⓘ FBXW7

                                     

ⓘ FBXW7

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs SKP1-cullin-F-box, which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class, in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers. These findings implicate the genes potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML and multiple myelomas require constitutive NF-κB signaling, therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.

Three variant transcripts encoding three different isoforms have been found for this gene.

                                     
  • repeat - containing protein 5 is a protein that in humans is encoded by the FBXW 5 gene. This gene encodes a member of the F - box protein family, members of
  • EML1, EML2, EML3, EML4, EML4 - ALK, EML5, ERCC8, FBXW 10, FBXW 11, FBXW 2, FBXW 4, FBXW 5, FBXW7 FBXW 8, FBXW 9, FZR1, GBL, GEMIN5, GNB1, GNB1L, GNB2, GNB2L1
  • repeat - containing protein 8 is a protein that in humans is encoded by the FBXW 8 gene. This gene encodes a member of the F - box protein family, members of
  • repeat - containing protein 4 is a protein that in humans is encoded by the FBXW 4 gene. This gene is a member of the F - box WD - 40 gene family, which recruit
  • repeat containing protein 2 also known as Fbxw 11 or HOS is a protein that in humans is encoded by the FBXW 11 F - box and WD repeat domain containing 11
  • activity by modulating expression of the FBXW7 protein. In particular, overexpression of miR - 223 reduces FBXW7 mRNA levels while increasing endogenous
  • homologue of the cdc4 gene is called FBXW7 The corresponding gene product is the F - box WD repeat - containing protein 7 In the nematode C. elegans, the homologue
  • is another mechanism. Loss - of - function mutations of FBXW7 were found in several cancer cells. FBXW7 encodes F - box proteins which target cyclin E for ubiquitination
  • In human colorectal carcinoma, RICTOR has been shown to association with FBXW7 outside of mTORC2 to mediate the ubiquitination of growth - promoting factors
  • ligases and kinases. FBXW7 a member of the SCF ubiquitin ligase family, targets NFE2L1 for proteolytic degradation by the proteasome. FBXW7 requires the Cdc4