F-box and WD repeat domain containing 10 (FBXW10)

F-box and WD repeat domain containing 10 (FBXW10) is a substrate recognition component of the SCF (SKP1–CUL1–F-box protein) E3 ubiquitin ligase complex, interacting with SKP1 through the F-box motif and conferring substrate specificity via its WD repeat domains[1][3][5][6]. It mediates ubiquitination and subsequent proteasomal degradation of regulatory targets involved in chromatin structure, DNA repair (e.g., HP1α/β, ATR kinase), and cell proliferation. FBXW10 is implicated in tumorigenesis—notably in hepatocellular carcinoma where high expression correlates with poor prognosis—and disorders such as spermatogenic failure and abnormalities in tooth eruption[3][5]. FBXW10 mutations have been linked to leukemia, and its expression is epigenetically regulated in various cancers. Pharmacological modulation by histone deacetylase inhibitors (such as belinostat) can enhance the degradation of oncogenic proteins via FBXW10, potentially sensitizing cancer cells to chemotherapy. Dysregulated FBXW10 function poses risks of inappropriate protein degradation, affecting genomic stability and cell survival[3][5].

Other names

F-box/WD repeat-containing protein 10Fbw10HREPSM2SH2SM25H2F-box and WD-40 domain-containing protein 10ubiquitin ligase-specificity factortesticular tissue protein Li 69FBXW10

Proteasomal degradation via E3 ubiquitin ligase activity, targeting specific substrates (e.g., CBX5, CBX1, HP1α/β, ATR kinase, SOS protein) for ubiquitin-dependent proteolysis