| 2019 |
RhoBTB1 acts as a substrate adaptor delivering phosphodiesterase 5 (PDE5) to the Cullin-3 (CUL3) E3 RING ubiquitin ligase complex, leading to PDE5 ubiquitination and inhibition, thereby augmenting cGMP responses to nitric oxide in vascular smooth muscle cells. |
Genetic complementation (inducible smooth muscle-specific RhoBTB1 transgene), Co-immunoprecipitation, functional vasodilation assays in vivo |
The Journal of clinical investigation |
High |
30896450
|
| 2023 |
The C-terminal half of RhoBTB1 (B1B2C region, comprising both BTB domains and C-terminal domain) is the minimal region required for PDE5 recruitment and subsequent proteasomal degradation via CUL3; the C-terminal domain is essential for PDE5 binding, and Pro353 and Ser363 are key residues required for CUL3 binding (mutation impairs CUL3 binding and PDE5 degradation without disrupting PDE5 binding). |
Domain truncation, Co-immunoprecipitation, site-directed mutagenesis, APEX2 proximity labeling/mass spectrometry |
Function (Oxford, England) |
High |
37575477
|
| 2023 |
SETD2 is a binding partner of RhoBTB1 (validated by Co-IP), and SETD2 levels increase upon proteasome inhibition, Cullin complex inhibition, CUL3 deletion, or RhoBTB1 siRNA knockdown, suggesting SETD2 is a substrate regulated by the RhoBTB1-CUL3 ubiquitin-proteasome axis. |
APEX2 proximity labeling/mass spectrometry, Co-immunoprecipitation, siRNA knockdown, pharmacological proteasome/Cullin inhibition |
Function (Oxford, England) |
Medium |
37575477
|
| 2022 |
RhoBTB1 reverses established arterial stiffness by promoting actin depolymerization in vascular smooth muscle; angiotensin II-induced actin polymerization in the aorta is reversed by RhoBTB1 restoration, with consistent changes in levels of cofilin and vasodilator-stimulated phosphoprotein (VASP), two regulators of actin polymerization. |
Inducible smooth muscle-specific RhoBTB1 transgene, measurement of actin polymerization, immunoblotting for cofilin and VASP, arterial stiffness measurements in vivo |
JCI insight |
High |
35358093
|
| 2026 |
RhoBTB1 interacts with and promotes CUL3-dependent ubiquitination and proteasomal degradation of RbFox2 in smooth muscle cells; loss of RhoBTB1 (by siRNA or angiotensin II) elevates RbFox2, and RbFox2 regulates actin cytoskeletal integrity and arterial stiffness. |
Co-immunoprecipitation, proximity labeling/mass spectrometry, siRNA knockdown, CUL3 deletion, RbFox2 floxed mouse model, ubiquitination assay |
JCI insight |
High |
41926228
|
| 2019 |
RhoBTB1 associates with ROCK1 and ROCK2; the interaction with ROCK1 is mediated by the Rho domain of RhoBTB1 binding to the coiled-coil region of ROCK1 near its kinase domain. Two amino acids in the Rho domain alter RhoBTB1-ROCK1 association. RhoBTB1 is a substrate for ROCK1, and mutation of putative ROCK1 phosphorylation sites on RhoBTB1 reduces its association with Cullin3. |
Co-immunoprecipitation, pulldown, site-directed mutagenesis, in vitro kinase assay |
The Biochemical journal |
High |
31431478
|
| 2019 |
RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2, suggesting RhoBTB1 suppresses cancer cell invasion through interaction with ROCKs. |
siRNA knockdown, Matrigel invasion assay, cell morphology imaging |
The Biochemical journal |
Medium |
31431478
|
| 2017 |
RhoBTB1 regulates the integrity of the Golgi complex through control of METTL7B expression; silencing of either RhoBTB1 or METTL7B leads to Golgi fragmentation, and restoration of RhoBTB1 expression rescues Golgi morphology and inhibits breast cancer cell invasion. |
Gene silencing (RNAi), transcriptome analysis, Q-PCR, cell imaging (Golgi morphology), rescue experiments |
BMC cancer |
Medium |
28219369
|
| 2020 |
RhoBTB1 localizes to early endosomal intermediates, and changes in RhoBTB1 levels cause disturbances to Golgi architecture, profound changes to organisation and distribution of endosomes and lysosomes, and defects in delivery of two classes of cargo molecules to downstream compartments, linking RhoBTB1 to endocytosis and retrograde traffic pathways. |
RNA interference screen, high-content image-based analysis, fluorescence microscopy, cargo trafficking assays |
Cells |
Medium |
32354068
|
| 2017 |
RhoBTB1 is a target gene of miR-31a-5p; miR-31a-5p promotes postnatal cardiomyocyte proliferation by repressing RhoBTB1, and RhoBTB1 knockdown phenocopies miR-31a-5p overexpression in promoting cardiomyocyte proliferation markers. |
miRNA arrays, luciferase reporter assay (implied by target validation), immunofluorescence, EdU/Ki-67/PHH3 proliferation assays, antagomir injection in neonatal rats |
Experimental & molecular medicine |
Medium |
29053138
|
| 2024 |
Exosomal miR-31 from cutaneous squamous cell carcinoma (CSCC) cells directly targets the 3'UTR of RhoBTB1 (validated by dual luciferase reporter assay), suppressing RhoBTB1 expression and enhancing CSCC cell proliferation, migration, and invasion. |
Dual luciferase reporter assay, immunoblotting, qPCR, MTT assay, Transwell assay, differential ultracentrifugation for exosome isolation |
Archives of dermatological research |
Medium |
39673615
|