| 2015 |
KBTBD7 (together with KBTBD6) functions as a substrate adaptor for a CUL3 RING ubiquitin ligase complex that mediates ubiquitylation and proteasomal degradation of TIAM1, a RAC1-specific GEF. Depletion of KBTBD6/7 elevates TIAM1 abundance, increases RAC1 activity, alters actin morphology, causes loss of focal adhesions, reduces proliferation, and enhances invasion. KBTBD7 employs ATG8 family-interacting motifs to bind preferentially to GABARAP proteins, and ubiquitylation of TIAM1 by CUL3-KBTBD6/KBTBD7 depends on GABARAP binding, revealing that recruitment to GABARAP-containing vesicles spatially restricts RAC1 signaling. |
Co-immunoprecipitation, ubiquitylation assays, siRNA knockdown with actin morphology/invasion/proliferation readouts, ATG8-family binding motif mutagenesis, vesicle recruitment assays |
Molecular cell |
High |
25684205 27308540
|
| 2021 |
KBTBD7 acts as an E3 ligase that is recruited by p97/VCP via UBA-UBX adaptors to promote ubiquitination and ERAD (endoplasmic reticulum-associated degradation) of the Wnt/PCP core components Vangl1 and Vangl2. Wnt5a/CK1-induced phosphorylation of Vangl prevents its ubiquitination by KBTBD7 and facilitates its export from the ER to the plasma membrane. In vivo, KBTBD7 regulates convergent extension during zebrafish gastrulation, consistent with its role in controlling Vangl abundance. |
Co-immunoprecipitation (p97/VCP–KBTBD7 and KBTBD7–Vangl interactions), ubiquitination assays, ERAD assays, phosphorylation-blocking mutants, zebrafish convergent-extension phenotype rescue/loss-of-function |
Science advances |
High |
33990333
|
| 2020 |
KBTBD7 directly interacts with and ubiquitinates dopamine type 2 receptor (DRD2) at five specific lysine residues (K221, K226, K241, K251, K258), targeting internalized DRD2 for proteasomal degradation. KBTBD7 knockout mice show elevated DRD2 protein in pituitary, thalamus, and heart. KBTBD7-mediated DRD2 degradation attenuates cabergoline-induced inhibition of the AKT/mTOR pathway, and knockdown of KBTBD6/7 sensitizes pituitary tumor cells to dopamine agonist treatment. |
Yeast two-hybrid, Co-IP, ubiquitination site mapping, CRISPR-Cas9 knockout mice with DRD2 protein quantification, cell-based knockdown/overexpression with AKT/mTOR signaling readouts |
Acta neuropathologica |
High |
32572597
|
| 2018 |
KBTBD7 is a direct target of miR-21 (validated by luciferase reporter assay) and promotes DAMP-triggered inflammatory responses in macrophages. KBTBD7 physically interacts with MKK3/6 and promotes their activation, which in turn enhances downstream p38 and NF-κB signaling induced by DAMPs (HMGB1 and HSP60). miR-21 deficiency elevates KBTBD7 expression and exacerbates this signaling axis post-MI. |
Luciferase reporter assay (miR-21 targeting of KBTBD7 3'UTR), Co-immunoprecipitation (KBTBD7–MKK3/6 interaction), miR-21 knockout mice, siRNA knockdown with cytokine and phospho-signaling readouts |
Cell death & disease |
Medium |
29991775
|
| 2022 |
KBTBD7 promotes ubiquitin-dependent proteasomal degradation of PTEN in non-small cell lung cancer cells, thereby activating EGFR/PI3K/AKT signaling and promoting cell proliferation and invasion. |
KBTBD7 knockdown in NSCLC cell lines with PTEN protein level measurement, ubiquitination assays, downstream signaling (AKT) and proliferation/invasion readouts |
Cancer medicine |
Medium |
35499228
|
| 2024 |
KBTBD7 acts as an E3 ubiquitin ligase that directly binds KLF15 transcription factor (confirmed by Co-IP) and catalyzes its ubiquitination and proteasomal degradation. Loss of KBTBD7 in LPS-treated microglia stabilizes KLF15, suppresses NLRP3 inflammasome and NF-κB signaling activation, and reduces pro-inflammatory cytokine release; KLF15 knockdown abolishes this anti-inflammatory effect. |
Co-immunoprecipitation (KBTBD7–KLF15), ubiquitination assays, siRNA knockdown with NLRP3/NF-κB signaling readouts, epistasis rescue experiment (KLF15 KD reverting KBTBD7 KD phenotype) |
Experimental cell research |
Medium |
39489209
|
| 2024 |
KBTBD7 interacts with FOXA1 and promotes FOXA1 expression, which indirectly inhibits SLC7A11 transcription; this axis drives ferroptosis and mitochondrial dysfunction in LPS-treated alveolar epithelial cells. KBTBD7 knockdown reduces ROS production, ferroptosis markers, and inflammatory cytokines in vitro and in a septic lung injury mouse model. |
Co-immunoprecipitation (KBTBD7–FOXA1), siRNA knockdown in LPS-induced cells and in vivo CLP model with ferroptosis/ROS/cytokine readouts |
International immunopharmacology |
Low |
38652964
|
| 2010 |
KBTBD7 protein (684 aa, 77 kDa) localizes to the cytoplasm in COS-7 cells. When fused to a GAL4 DNA-binding domain, KBTBD7 activates transcription; deletion analysis shows the BTB domain and kelch repeat motif are the main regions for transcriptional activation. Overexpression in MCF-7 cells activates AP-1 and SRE transcriptional activities, an effect reversed by siRNA knockdown. |
Western blot (expression/localization), GAL4-fusion transcription assay, deletion constructs, AP-1/SRE luciferase reporter assays, siRNA knockdown |
BMB reports |
Medium |
20132730
|