Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure

Wu, Jing; McCormick, James A.

doi:10.1007/s11906-020-01076-8

Cited by 11 publications

(9 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, several studies have identified various E3 ligases targeting RhoA for degradation. For example a role for Cullin3-based ubiquitin ligases targeting RhoA, both in smooth muscle cells as well as in neurons, has been described (Wu, McCormick, and Sigmund 2020; Escamilla et al 2017). Apparently, under these conditions, GAP-dependent inactivation is insufficient to limit RhoA signaling, and ubiquitin-mediated degradation is prevalent.…”

Section: Discussionmentioning

confidence: 99%

Rapid proteostasis controls monolayer integrity of quiescent endothelium

Podieh

Wensveen

Overboom

et al. 2022

Preprint

View full text Add to dashboard Cite

Endothelial monolayer permeability is regulated by actin dynamics and vesicular traffic. Recently, ubiquitination was also implicated in the integrity of quiescent endothelium, as it differentially controls the localization and stability of adhesion- and signaling proteins. We found that inhibition of E1 ubiquitin ligases induces a rapid, reversible loss of integrity in quiescent, primary human endothelial monolayers, accompanied by increased F-actin stress fibers and the formation of intercellular gaps. Concomitantly, total protein and activity of the actin-regulating GTPase RhoB, but not its close homologue RhoA, increase ~10-fold in 5-8 h. The depletion of RhoB, but not of RhoA, the inhibition of actin contractility and the inhibition of protein synthesis all significantly rescue the loss of cell-cell contact induced by E1 ligase inhibition. Our data suggest that in quiescent human endothelial cells, the continuous and fast turnover of short-lived proteins that negatively regulate cell-cell contact, is essential to preserve monolayer integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Rapid proteostasis controls monolayer integrity of quiescent endothelium

Podieh

Wensveen

Overboom

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The ROCKs inhibitor fasudil improved the MCT-induced improvement in PAH by inhibiting PASMC proliferation and reducing macrophage infiltration [77][78][79] . It was shown that loss of Cullin3 led to disturbed RhoA stability, increased ROCKs activity, vasoconstriction and hypertension 80,81 . Therefore, the enhanced Cullin3 function and inhibition of the RhoA/ROCKs pathway can induce PASMC relaxation and control vasodilation, and it may be a novel pathway to prevent PAH.…”

Section: Cullin3-bacurdmentioning

confidence: 99%

Investigation of the ubiquitin proteasome system in pulmonary arterial hypertension

Li¹,

Bian²,

Gu³

et al. 2023

Preprint

View full text Add to dashboard Cite

Ubiquitin proteasome system (UPS) is the major avenues approach of protein degradation, which is responsible for 80% protein degradation in eukaryotic cells. Recently, UPS is involved in a variety of disease processes and plays a significant role in DNA repair, transcription regulation, autophagy and protein transport. Pulmonary arterial hypertension (PAH) is a disease mainly caused by pulmonary artery endothelial cell (PAEC) dysfunction and pulmonary artery smooth muscle cell (PASMC) excessive proliferation and abnormal apoptosis. These increased pulmonary vascular resistance, vascular remodeling, and finally leading to the failure of right heart. The alteration of pulmonary artery protein ubiquitination occurs at the initial stage of PAH and participates in several cell pathways, such as vasoconstriction, tissue remodeling/angiogenesis, cell migration and calcium signaling. In this review, we mainly introduce the functional changes of UPS in PAH, especially specific E3 ubiquitin ligases with related endoplasmic reticulum stress (ERS), proteolysis-targeting chimeras (PROTACs) and proteasome inhibitors mediated degradation mechanism, providing new ideas for the precise diagnosis and treatment of PAH.

show abstract

“…CUL3 has been shown to play a significant role in the cardiovascular system, particularly in regulating blood pressure [89][90][91][92][93][94][95][96][97][98]. Tissue-specific deletion of the cul3 gene in mouse skeletal muscle cells or cardiomyocytes led to neonatal lethality, because of skeletal muscle dysfunction or severe cardiomyopathy [91].…”

Section: Cul3 Mutations and Cardiovascular Diseasesmentioning

confidence: 99%

Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases

et al. 2022

View full text Add to dashboard Cite

Maintenance of protein homeostasis is crucial for virtually every aspect of eukaryotic biology. The ubiquitin-proteasome system (UPS) represents a highly regulated quality control machinery that protects cells from a variety of stress conditions as well as toxic proteins. A large body of evidence has shown that UPS dysfunction contributes to the pathogenesis of cardiovascular diseases. This review highlights the latest findings regarding the physiological and pathological roles of cullin-RING ubiquitin ligases (CRLs), an essential player in the UPS, in the cardiovascular system. To inspire potential therapeutic invention, factors regulating CRL activities are also discussed.

show abstract

Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure

Cited by 11 publications

References 59 publications

Rapid proteostasis controls monolayer integrity of quiescent endothelium

Rapid proteostasis controls monolayer integrity of quiescent endothelium

Investigation of the ubiquitin proteasome system in pulmonary arterial hypertension

Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases

Contact Info

Product

Resources

About