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Omics · study · 2026

RbFox2 is a RhoBTB1-Cullin-3 Target in Vascular Smooth Muscle Regulating Arterial Stiffness through the Cytoskeleton

Listed in NCBI GEO

The RhoBTB1-Cullin3 (CUL3) pathway in smooth muscle cells (SMCs) controls the ubiquitination of target proteins and through this blood pressure (BP) and arterial stiffness.

Description

We performed proximity labelling coupled with mass spectrometry to identify RhoBTB1 interacting partners in A7R5 SMCs. We identified 59 proteins which bound to the C-terminal half of RhoBTB1, the region identified as essential for its adapter function to deliver substrates to CUL3.

We examined one of these proteins in detail - RbFox2. Co-immunoprecipitation validated the interaction of RbFox2 with RhoBTB1. Expression of RbFox2 was elevated in response to inhibition of the ubiquitination-proteasomal pathway, CUL3-deficiency, and RhoBTB1 inhibition by either siRNA or angiotensin II (ANG).

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RbFox2 was ubiquitinated in a RhoBTB1- and CUL3-dependent manner suggesting it is regulated through the RhoBTB1-CUL3-dependent ubiquitin-proteasome pathway. Inhibition of RbFox2 impaired the actin cytoskeleton in A7R5 cells and in primary SMC from RbFox2Flox mice and decreased the levels of globular and filamentous actin. ANG increased BP and arterial stiffness of RbFox2Flox mice, but the progression of arterial stiffness was halted after SMC-specific RbFox2 deletion despite a continued rise in BP.

We conclude that RhoBTB1 and its target RbFox2 is an important regulator of arterial stiffness through its actions to regulate the cytoskeleton.

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Life Sciences
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Mass spectrometry 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30590115 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:mass-spectrometryenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10116source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title