| 2004 |
FBXO38 (MoKA) physically interacts with KLF7 transcription factor, confirmed by GST pull-down and co-immunoprecipitation, and functions as a KLF7 coactivator to stimulate transcription of target genes including p21(WAF1/Cip1). Distinct structural motifs of FBXO38 mediate KLF7 interaction and nucleocytoplasmic shuttling. |
Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, chromatin immunoprecipitation, transient transfection reporter assays |
Molecular and cellular biology |
High |
14729953
|
| 2006 |
FBXO38 (MoKA) shuttles between nucleus and cytoplasm via a single functional NLS recognized by karyopherin receptors and three distinct cytoplasmic retention/export sequences: one CRM1-dependent leucine-rich NES and two CRM1-independent export signals. The major transcriptional activation domain maps to a highly acidic sequence between the NLS and NES clusters. |
Forced expression of fusion proteins in mammalian cells, nuclear export inhibitor (leptomycin B) treatment, deletion/mutation analysis, GAL4 chimeric transcriptional assays |
Nucleic acids research |
High |
16990251
|
| 2013 |
The FBXO38 p.Cys206Arg missense mutation impairs KLF7-mediated transactivation of a KLF7-responsive promoter and endogenous KLF7 target genes without altering subcellular localization of FBXO38, and this transcriptional dysregulation is associated with impaired neurite outgrowth in primary motor neurons. |
Transient transfection reporter assays in HEK293T cells, fibroblasts from patients with the mutation, primary motor neuron neurite outgrowth assay |
American journal of human genetics |
Medium |
24207122
|
| 2018 |
FBXO38 is an E3 ubiquitin ligase that mediates Lys48-linked poly-ubiquitination of PD-1 and subsequent proteasome-dependent degradation after PD-1 internalization in activated T cells. Conditional T cell-specific Fbxo38 knockout led to elevated PD-1 on tumor-infiltrating T cells and faster tumor progression in mice, which was normalized by anti-PD-1 therapy. |
E3 ligase identification, ubiquitination assay (Lys48-linkage specificity), conditional knockout mice, tumor growth assays, anti-PD-1 rescue experiment |
Nature |
High |
30487606
|
| 2019 |
USP7 deubiquitylase stabilizes FBXO38 by protecting it from proteasomal degradation in a catalytic-activity-dependent manner. FBXO38 in turn stabilizes KIF20B (a Kinesin-6 required for cytokinesis) independently of an SCF complex. Depletion of either USP7 or FBXO38 reduces KIF20B levels and its midbody localization, causing cytokinetic defects; these defects are rescued by restoring FBXO38 or KIF20B. |
Affinity purification-mass spectrometry, BioID proximity labeling, co-immunoprecipitation, siRNA knockdown, proteasome inhibitor treatment, cytokinesis phenotype assay, rescue experiments |
Scientific reports |
High |
30804394
|
| 2022 |
FBXO38 functions as the substrate receptor of the SCF(FBXO38) E3 ubiquitin ligase complex and directly promotes ubiquitination and proteasome-dependent degradation of zinc finger proteins ZXDA and ZXDB. ZXDA/B associate with centromeric protein CENP-B, and their stabilization upon FBXO38 loss leads to upregulation of CENP-A and CENP-B positive centromeric chromatin, establishing a role for cullin-dependent degradation in centromere integrity control. |
Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, chromatin immunoprecipitation, mutant cell analysis |
Frontiers in cell and developmental biology |
High |
35813202
|
| 2022 |
In Sertoli cells, FBXO38 controls centromeric chromatin integrity through ZXDB degradation. Loss of FBXO38 in mice causes ZXDB stabilization, upregulated centromeric chromatin, defective Sertoli cell maturation (dysregulation of retinoic acid metabolism and intercellular communication genes), and impaired spermatogonial differentiation, leading to reduced sperm production and fertility. |
Fbxo38 conditional knockout mice, immunofluorescence, gene expression profiling, histological analysis of testes |
Frontiers in cell and developmental biology |
High |
35769260
|
| 2023 |
FBXO38 promotes macrophage immunosuppressive (M2-like) polarization by upregulating M2-like gene expression via MAPK and IRF4 signaling pathways, without affecting M1-like polarization. Fbxo38 deletion in macrophages blocks tumor development and protects against DSS-induced colitis in mice. |
Macrophage-specific conditional knockout mice, tumor growth assay, DSS colitis model, gene expression analysis, pathway analysis (MAPK/IRF4) |
Cellular & molecular immunology |
Medium |
37821621
|
| 2023 |
FBXO38 interacts with and ubiquitylates FGL1, promoting its proteasome-dependent degradation. Depletion of FBXO38 markedly increases FGL1 abundance, suppresses CD8+ T cell infiltration, and enhances immune evasion. Additionally, FBXO38 deficiency increases IL-6 levels in vivo and in cancer specimens. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vitro and in vivo tumor models, correlation analysis in patient specimens |
Cell reports |
Medium |
37938970
|
| 2024 |
FBXO38 deficiency reduces STING protein levels through lysosome-mediated (not proteasomal) degradation, thereby inhibiting cGAS-STING pathway activation, reducing downstream IFNA1 and CCL5 production, enhancing tumor proliferation, and reducing CD8+ T cell infiltration. |
siRNA knockdown, in vitro and in vivo tumor models, lysosome inhibitor vs. proteasome inhibitor treatment, pathway activation assays (IFNA1, CCL5 measurement) |
Neoplasia |
Medium |
38277817
|
| 2024 |
FBXO38 is dispensable for PD-1 regulation in T cells. Experimental re-examination failed to support the notion that SCF(FBXO38) directly or indirectly controls the abundance and stability of PD-1 in T cells, contradicting the earlier report (PMID:30487606). |
Genetic T cell-specific knockout/re-examination, protein stability assays in T cells |
EMBO reports |
Medium |
39266770
|
| 2024 |
FBXO38 deficiency in NK cells enhances TGF-β signaling (elevating Smad2 and Smad3), which suppresses expression of transcription factor Eomes and reduces surface IL15Rβ and IL15Rγc expression on NK cells, leading to NK cell hyporesponsiveness to IL-15 and impaired proliferation/survival. FBXO38 overexpression in human NK cells enhances antitumor activity in vivo. |
NK-cell-specific conditional knockout mice, tumor growth and metastasis assays, flow cytometry, gene expression analysis, adoptive transfer of FBXO38-overexpressing human NK cells |
Cancer immunology research |
Medium |
38990095
|
| 2025 |
FBXO38 directly interacts with NADPH oxidase Nox1 and promotes its ubiquitin-proteasome-dependent degradation in endothelial cells. Under low oscillatory shear stress, FBXO38 protein levels are reduced (~60%), leading to Nox1 accumulation (~2-fold), increased ROS production, and endothelial apoptosis. FBXO38 overexpression attenuates Nox1 accumulation and reduces ROS under these conditions. |
Co-immunoprecipitation, overexpression and knockdown in HUVECs, in vitro shear stress model, in vivo partial carotid ligation mouse model, western blotting, immunofluorescence |
Cardiovascular therapeutics |
Medium |
40313652
|