PXD067797-1

PXD067797 is an original dataset announced via ProteomeXchange.

Title	RhoBTB1 C-Terminal Binding Proteins in A7r5 Smooth Muscle Cells
Description	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. We performed APEX2 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). 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.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-06_09:28:19.363.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD067797
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Curt Sigmund
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-27 09:04:36	ID requested
⏵ 1	2026-04-06 09:28:20	announced

10.6019/PXD067797;

10.1172/jci.insight.202638;

Kumar G, Chaihongsa N, Brozoski DT, Golosova D, Vazirabad I, Lu KT, Wackman KK, Singh RK, Sigmund CD, Vascular smooth muscle RbFox2 regulates the cytoskeleton and arterial stiffness by a RhoBTB1/Cullin-3 mechanism. JCI Insight, 11(11):(2026) [pubmed]

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Human Proteome Project

submitter keyword: Proximity Ligation, RHOBTB1,APEX2

Curt Sigmund
contact affiliation	Department of Physiology, Medical College of Wisconsin, USA
contact email	csigmund@mcw.edu
lab head
Curt Sigmund
contact affiliation	Department of Physiology Medical College of Wisconsin
contact email	csigmund@mcw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067797
     1. Label: PRIDE project
     2. Name: RhoBTB1 C-Terminal Binding Proteins in A7r5 Smooth Muscle Cells