F-box only protein 16 (FBXO16)

F-box only protein 16 (FBXO16) is a substrate-recognition component of the SCF (SKP1–Cullin1–F-box) E3 ubiquitin ligase complex, characterized by its F-box domain, which enables binding to SKP1[1][3]. FBXO16 targets specific nuclear proteins—including nuclear β-catenin and the p65 subunit of NF-κB—for ubiquitination and subsequent proteasomal degradation[2][3][5]. FBXO16 functions as a tumor suppressor by maintaining low nuclear β-catenin levels, thus inhibiting cancer cell proliferation, migration, invasion, and EMT; this action is independent of canonical β-catenin degradation mechanisms and specific to the nuclear compartment[1][3]. FBXO16 also negatively regulates inflammatory responses in dendritic cells by mediating p65 degradation in the context of an alternative E3 ligase complex[2][5]. Loss or reduced expression of FBXO16 is correlated with cancer progression and elevated inflammatory signaling[1][2][3]. FBXO16 has a nuclear localization signal necessary for its activity on nuclear substrates[1][3], and its diverse interactome suggests further biological roles that are not yet fully elucidated[1]. No drugs directly targeting FBXO16 are currently available, but modulation of its expression or function represents a potential therapeutic approach in oncology and immunology.

Other names

FBX16F-box protein 16F-box only protein 16FBXO16

Drugs would most likely act via modulation of substrate recognition or activity of the FBXO16-containing SCF E3 ligase complex, leading to altered proteasomal degradation of nuclear β-catenin or NF-κB p65 subunit. No specific drugs currently reported to directly target FBXO16.