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 , 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 .
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 .
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 .
BRAF and FBXW7 (CDC4, FBW7
, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets.