FBXW7


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FBXW7

A gene on chromosome 4q31.3 that encodes a so-called F-box protein, which contains a 40 amino acid protein-interacting motif (the F box). F-box proteins form a complex with SKP1 and cullin, resulting in phosphorylation-dependent ubiquitination and ubiquitin-mediated degradation of targeted proteins. F-box proteins are divided into three classes based on the presence of:
(1) WD-40 repeats—as is the case with this F-box protein (Fbws class),
(2) leucine-rich repeats (Fbls class); or
(3) the presence or absence of other protein-protein interacting domains (Fbxs class).
The FBXW7 protein product binds directly to cyclin E, targeting it for ubiquitin-mediated degradation.

Molecular pathology
FBXW7 mutations are found in ovarian and breast cancer cell lines, implicating FBXW7’s potential role in carcinogenesis.
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of Gene subgroup SMGs symbol Hypermutated/ 21 PTEN microsatellite- PIK3CA unstable PIK3R1 ARID1A RPL22 KRAS ZFHX3 ARID5B CTCF CTNNB1 ATR GIGYF2 CSDE1 FGFR2 CCND1 LIMCH1 RBMX NKAP HIST1H2BD TNFAIP6 MIR1277 Copy number low/ 16 PTEN microsatellite- PIK3CA stable CTNNB1 ARID1A PIK3R1 CTCF KRAS FGFR2 CHD4 SPOP CSMD3 (b) SOX17 SGK1 BCOR MECOM METTL14 Copy number high 8 TP53 (serous-like) PIK3CA FBXW7 PPP2R1A PIK3R1 CHD4 PTEN CSMD3 (b) Molecular Gene name Somatic-mutation subgroup frequency Hypermutated/ Phosphatase and tensin homolog 87.
Extensive study into the genetic profile of colorectal adenocarcinoma by TCGA identified the 8 most frequently mutated genes (APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, TCF7L2, and NRAS) (7); mutations in all of these genes (except for TCF7L2) were also identified in our rectal adenocarcinoma-based study.
The panel contains probes to generate 212 amplicons from 48 cancer-related genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, and VHL.
7 Based on the frequency of genetically affected genes in pancreatic cancers, a genetic "topographic map" of the pancreatic cancers can be generated in which the most frequent mutations are represented as 4 "mountains" (high-frequency driver genes) involving KRAS2, CDKN2A/p16, SMAD4/DPC4, and TP53, with numerous "hills" (low-frequency driver genes) involving SMARC4A, CDH1, EPHA3, FBXW7, EGFR, IDH1, and NF1.