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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References in periodicals archive ?
GSK30 inhibitor treatment or the GSK3[beta] S350A mutant stabilizes Nrf1, because the phosphorylation of Ser350 by GSK3[beta] is required for F-box/WD repeat-containing protein 7 (FBW7)dependent Nrf1 degradation.
(2011) The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1 transcription factor turnover through proteasome-mediated proteolysis.
This means that, in a MYC-overexpression condition, like GC [7], not only this gene and its protein are more produced, but they are also less destroyed because it diminishes the expression of E3 ubiquitin-ligases, such as Fbw7 and HectH9, contributing to prolonged MYC protein half-life and amplification of its effects [55].
Spencer-Dene et al., "The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer," The Journal of Clinical Investigation, vol.
Chan, "The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1 transcription factor turnover through proteasome-mediated proteolysis," Journal of Biological Chemistry, vol.
Li, "Role of the ubiquitin ligase Fbw7 in cancer progression," Cancer Metastasis Reviews, vol.
Clurman, "Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities," Cancer Cell, vol.
Mo et al., "The intracellular domain of Jagged-1 interacts with Notch1 intracellular domain and promotes its degradation through Fbw7 E3 ligase," Experimental Cell Research, vol.
Both the [alpha] and [beta] isoforms of p63 contain a phosphodegron motif utilized by Fbw7 E3 ubiquitin ligase in MDM2-mediated degradation [15].
D'Alessandra et al., "MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation," Journal of Cell Science, vol.
recently showed that vincristine-induced apoptosis is mediated by the molecular partnership between the ubiquitin-ligase FBW7 and MCL1, once it has been phosphorylated, downstream of vincristine treatment [42].
BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets.