Journal ArticleDOI
APC/Cdh1 targets PECAM‐1 for ubiquitination and degradation in endothelial cells
Jia Liu,Qinyu Yao,Lei Xiao,Fan Li,Wen Ma,Zihui Zhang,Xinya Xie,Chunmiao Yang,Qi Cui,Ying Tian,Chao Zhang,Baochang Lai,Nanping Wang +12 more
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TLDR
This study revealed a novel mechanism by which fluid flow patterns regulate EC homeostasis via Cdh1‐dependent ubiquitination and subsequent degradation of PECAM‐1 through the use of APC/Cdh1 E3 ubiquitin ligase.Abstract:
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin superfamily and is expressed by hematopoietic and endothelial cells (ECs). Recent studies have shown that PECAM-1 plays a crucial role in promoting the development of the EC inflammatory response in the context of disturbed flow. However, the mechanistic pathways that control PECAM-1 protein stability remain largely unclear. Here, we identified PECAM-1 as a novel substrate of the APC/Cdh1 E3 ubiquitin ligase. Specifically, lentivirus-mediated Cdh1 depletion stabilized PECAM-1 in ECs. Conversely, overexpression of Cdh1 destabilized PECAM-1. The proteasome inhibitor MG132 blocked Cdh1-mediated PECAM-1 degradation. In addition, Cdh1 promoted K48-linked polyubiquitination of PECAM-1 in a destruction box-dependent manner. Furthermore, we demonstrated that compared with pulsatile shear stress (PS), oscillatory shear stress decreased the expression of Cdh1 and the ubiquitination of PECAM-1, therefore stabilizing PECAM-1 to promote inflammation in ECs. Hence, our study revealed a novel mechanism by which fluid flow patterns regulate EC homeostasis via Cdh1-dependent ubiquitination and subsequent degradation of PECAM-1.read more
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Erratum: Cubism and the cell cycle: the many faces of the APC/C
TL;DR: This paper presents a new approach to cell reprograming that allows for real-time, 3D image analysis of the response of the H2O2+ “spatially reprogramed” response to EMT.
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Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy.
Qingyu Liang,Jianqi Wu,Xin Zhao,Shuai Shen,Chen Zhu,Tianqi Liu,Xiao Cui,Ling Chen,Chunmi Wei,Peng Cheng,Wen Cheng,Anhua Wu +11 more
TL;DR: In this paper, a systematical investigation on inflammasome signaling in various tumor types was conducted, which highlighted the importance of infmasome evaluation in tumor classification and provided a foundation for improving relevant therapeutic regimens.
Journal ArticleDOI
The role of tumor necrosis factor-α and interferon-γ in the hyperglycemia-induced ubiquitination and loss of platelet endothelial cell adhesion molecule-1 in rat retinal endothelial cells.
Randa S. Eshaq,Norman R. Harris +1 more
TL;DR: In this article, the role of hyperglycemia-induced increase in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the ubiquitination and degradation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in diabetic retina was investigated.
Journal ArticleDOI
Identification of Somatic Mutation-Driven Immune Cells by Integrating Genomic and Transcriptome Data
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Journal ArticleDOI
Frataxin inhibits the sensitivity of the myocardium to ferroptosis by regulating iron homeostasis.
TL;DR: In this paper , the authors used LC-MS/MS to identify potential E3 ligases that interacted with frataxin in heart tissue, and found that the resulting increased levels of iron metabolism were differentially expressed in the ischemic and reperfused myocardium and involved in regulation of cardiomyocytes ferroptosis.
References
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Journal ArticleDOI
Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives
Jeng Jiann Chiu,Shu Chien +1 more
TL;DR: Current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications are summarized to contribute to the understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
Journal ArticleDOI
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Eleni Tzima,Mohamad Irani-Tehrani,William B. Kiosses,Elizabetta Dejana,David A. Schultz,Britta Engelhardt,Gaoyuan Cao,Horace M. DeLisser,Martin A. Schwartz,Martin A. Schwartz +9 more
TL;DR: In this paper, the authors investigated the pathway upstream of integrin activation and found that PECAM-1 and VEGFR2 are sufficient to confer responsiveness to flow in heterologous cells.
Journal ArticleDOI
The anaphase promoting complex/cyclosome: a machine designed to destroy
TL;DR: Recent discoveries have revealed an unexpected multitude of mechanisms that control APC/C activity, and have provided a first insight into how this unusual ubiquitin ligase recognizes its substrates.
Journal ArticleDOI
Mechanotransduction in vascular physiology and atherogenesis
Cornelia Hahn,Martin A. Schwartz +1 more
TL;DR: This work has highlighted the potential endothelial mechanotransducers that might mediate responses to blood flow, the effects of atheroprotective rather than atherogenic flow,The mechanisms that contribute to the progression of the disease and how systemic factors interact with flow patterns to cause atherosclerosis.
Journal ArticleDOI
Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress
Caroline Cheng,Dennie Tempel,Rien van Haperen,Arjen van der Baan,Frank Grosveld,Mat J.A.P. Daemen,Rob Krams,Rini de Crom +7 more
TL;DR: A perivascular shear stress modifier is developed that induces regions of lowered, increased, and lowered/oscillatory (ie, with vortices) shear stresses in mouse carotid arteries and studied plaque formation and composition, finding lowered shear stressed lesions induce larger lesions with a vulnerable plaque phenotype.
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