F-box and WD repeat domain containing 9 (FBXW9)

F-box and WD repeat domain containing 9 (FBXW9) is a member of the F-box protein family distinguished by a conserved F-box motif and multiple WD40 repeat domains, functioning as the substrate-recognition component in SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complexes[1][2][3]. FBXW9 mediates the ubiquitination and subsequent proteasomal degradation of specific protein substrates, influencing central cellular processes such as cell cycle progression and proliferation[2][3][4]. FBXW9 is notably upregulated in several human cancers, most prominently in breast cancer, where its expression correlates with poor prognosis, cancer cell stemness, and resistance to immune therapies such as anti-PD1 agents[2]. Mechanistically, FBXW9 targets key cell cycle and cancer-related proteins (e.g., TP53 pathway, MYC axis) for ubiquitination, thus impacting cell proliferation, tumor progression, and the tumor microenvironment[2]. FBXW9 is currently regarded as a potential therapeutic target and biomarker in oncology, particularly for breast cancer and potentially other malignancies[2].

Other names

F-box/WD repeat-containing protein 9FBW9MGC10870Fbw9MEC-15F-box and WD-40 domain-containing protein 9specificity factor for SCF ubiquitin ligase

Protein ubiquitination leading to targeted substrate degradation, Regulation of TP53 pathway and cell cycle progression