| 2015 |
SCF-FBXO24 acts as a ubiquitin E3 ligase that polyubiquitinates NDPK-A at K85, targeting it for proteasomal degradation. The interaction requires NDPK-A residues L55 and K56; K56 acetylation by GCN5 impairs FBXO24 binding and stabilizes NDPK-A, while GCN5 depletion accelerates NDPK-A degradation. FBXO24 silencing or expression of an acetylation mimic increases NDPK-A lifespan and impairs cell migration and wound healing. |
Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (K85R, K56Q acetylation mimic), cycloheximide chase, GCN5 knockdown, wound-healing/migration assay |
Molecular and cellular biology |
High |
25582197
|
| 2020 |
FBXO24 binds PRMT6 at residues 270–275 and mediates K48-linked polyubiquitination of PRMT6 at K369, targeting it for proteasomal degradation. A K369R PRMT6 mutant is resistant to degradation, and PRMT6 K369R overexpression drives cell cycle progression and proliferation. FBXO24 overexpression or PRMT6 knockout inhibits cell proliferation, migration, and invasion in H1299 cells. |
Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K369R), cycloheximide chase, cell proliferation/migration/invasion assays, FBXO24 overexpression and PRMT6 knockout |
Biochemical and biophysical research communications |
Medium |
32828318
|
| 2023 |
FBXO24 functions as an E3 ligase that ubiquitinates LSD1 (KDM1A), targeting it for proteasomal degradation. Identified via unbiased siRNA screen of all human SCF family E3 ligases; FBXO24 inhibits LSD1-induced tumorigenesis and acts as a tumor suppressor in breast cancer cells. |
Unbiased siRNA screen targeting SCF E3 ligases, Co-immunoprecipitation, ubiquitination assay, FBXO24 knockdown/overexpression with LSD1 protein stability and tumorigenesis readouts |
Molecular cancer research : MCR |
Medium |
37540490
|
| 2024 |
FBXO24 interacts with splicing factors SRSF2, SRSF3, and SRSF9 to modulate alternative splicing of mRNAs in round spermatids. FBXO24 genetic knockout in mice causes widespread aberrant splicing events affecting genes critical for sperm formation, leading to abnormal histone retention, incomplete axonemes, oversized chromatoid body, and abnormal mitochondrial coiling, resulting in male sterility. Additionally, FBXO24 interacts with MIWI and SCF subunits to mediate K48-linked polyubiquitination and degradation of MIWI, and FBXO24 depletion causes aberrant piRNA production. |
Co-immunoprecipitation (FBXO24 with SRSF2/3/9 and MIWI), genetic knockout mice, RNA-seq (alternative splicing analysis), ubiquitination assay (K48-linked), sperm morphology/motility analysis, piRNA profiling |
eLife |
High |
38470475
|
| 2024 |
FBXO24 ubiquitinates IPO5 (importin-5) in male germ cells. FBXO24 knockout in mice causes abnormal accumulation of RNAs, IPO5, and KPNB1 in sperm flagella and formation of aberrant membraneless electron-dense RNP granules, leading to malformed flagellar structures, impaired sperm motility, and male infertility. IPO5 and KPNB1 associate with stress granules upon oxidative stress or proteasome inhibition, suggesting FBXO24-driven IPO5 degradation prevents aberrant granule accumulation. |
FBXO24 knockout mice, in vivo ubiquitination assay for IPO5, electron microscopy, immunofluorescence/localization of RNP proteins, proteasome inhibitor and oxidative stress treatments |
eLife |
High |
37986737 39163107
|
| 2024 |
FBXO24 targets FOXK2 transcription factor for polyubiquitylation and proteasomal degradation in lung epithelia. FOXK2 binds FBXO24 through its carboxyl terminus (aa 428–478), undergoes multisite polyubiquitylation, and is degraded in the nucleus. FOXK2 localizes to mitochondria, and its depletion or expression of C-terminal deletion mutants impairs mitochondrial function. In experimental bacterial pneumonia, Fbxo24 heterozygous mice show preserved FOXK2 levels and mitochondrial function compared to WT littermates. |
Co-immunoprecipitation, ubiquitination assay, deletion mutagenesis of FOXK2 C-terminus, cycloheximide chase, mitochondrial function assays, Fbxo24 heterozygous mouse model with bacterial pneumonia |
The Journal of biological chemistry |
High |
38735474
|
| 2025 |
FBXO24 mediates K6-linked polyubiquitylation of SLC25A26 (mitochondrial S-adenosylmethionine transporter) at K31, targeting it for degradation. In Fbxo24 knockout mice, elevated SLC25A26 causes mitochondrial fragmentation, disorganized mitochondrial clustering, reduced mitochondrial membrane potential, elevated ROS, and suppressed glycolysis and oxidative phosphorylation, leading to decreased ATP production, sperm motility defects, and male infertility. |
Fbxo24 knockout mice, quantitative proteomics to identify substrates, in vitro/in vivo ubiquitination assay with linkage analysis (K6), site-directed mutagenesis (K31R), mitochondrial function assays (membrane potential, ROS, ATP production, glycolysis/OXPHOS) |
Development (Cambridge, England) |
High |
40657752
|
| 2025 |
FBXO24 (as part of SCF complex) ubiquitinates FoxP1 via K48- and K63-linked polyubiquitination, co-localizing with FoxP1 in the nucleus of lung epithelial cells. FBXO24 depletion stabilizes FoxP1 and reverses FoxP1-loss-induced unfolded protein response and cell death. Fbxo24 KO mice show elevated FoxP1 in lung and heart and reduced UPR after cigarette smoke exposure. Reciprocally, FoxP1 protein binds the FBXO24 promoter to suppress FBXO24 transcription. |
Co-immunoprecipitation, nuclear co-localization (imaging), FBXO24 knockdown/KO with FoxP1 stability and UPR readouts, Fbxo24 KO mouse model, FBXO24 promoter binding assay for FoxP1 |
bioRxivpreprint |
Medium |
40501863
|