Evidence map›Paper›PMID 40955569›Full record

ArticleCirculation2025

TAX1BP3 Is a SUMOylated Nucleocytoplasmic Shuttling Protein and Protects Against Vascular Neointimal Hyperplasia.

Hanyan Yang, Yulong Zhong, Wenjie Guo, Wenjing Guo, Boliang Chen, Zexuan Lin, Qin Zhang, Rongjun Zou, Xiaolong Cao, Fengxian Li and 10 more

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Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Hanyan Yang *Department of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Yulong Zhong *Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China (Y.Z., S.A.).ORCID 0009-0000-3029-0641
Wenjie Guo *Department of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Wenjing Guo *Department of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Boliang ChenDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Zexuan LinDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Qin ZhangDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China (Q.Z.).
Rongjun ZouDepartment of Cardiovascular Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (R.Z., X. Fan).ORCID 0000-0003-1981-5472
Xiaolong CaoDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).ORCID 0000-0001-8124-7491
Fengxian LiDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (X.C., F.L.).ORCID 0000-0002-3307-1468
Wei FengDepartment of Medicine, University of California San Diego, La Jolla, CA (W.F., X. Fang).ORCID 0000-0002-9106-4258
Jianyun YanDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).ORCID 0000-0002-6962-1169
Zhi ZengDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).ORCID 0000-0002-5687-5610
Wei WangInterventional Medicine Department, Shandong University, Jinan, Shandong, China (W.W.).ORCID 0000-0002-6346-2216
Kunfu OuyangDepartment of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China (K.O.).ORCID 0000-0003-0292-375X
Xinjie XuState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (X.X.).
Xiaoping FanDepartment of Cardiovascular Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (R.Z., X. Fan).ORCID 0000-0002-7067-7450
Xi FangDepartment of Medicine, University of California San Diego, La Jolla, CA (W.F., X. Fang).ORCID 0000-0001-7816-8821
Shanshan AiDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).
Canzhao LiuDepartment of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).ORCID 0000-0002-9035-5723

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeointimal hyperplasia is the major cause of significant vascular complications after arterial interventions. Despite the advancements in strategies such as drug-eluting stents to minimize neointimal hyperplasia, achieving consistently effective long-term outcomes remains a challenge. Protein-protein interactions mediated by PDZ (PSD-95, Discs-large, and ZO-1) domains are essential for numerous biological processes. However, little is known about the role of PDZ proteins in neointima formation. This study aims to explore the role of TAX1BP3 (Tax1 binding protein 3), a singular PDZ protein, in phenotypic switching of vascular smooth muscle cells (VSMCs) and its implication in neointimal hyperplasia.

methodsSubcellular localization of TAX1BP3 was assessed in isolated VSMCs or arteries obtained from mice with neointima formation. TAX1BP3 mutants were constructed to study the role of SUMOylation on TAX1BP3 nucleocytoplasmic shuttling. VSMC-specific Tax1bp3 knockout mice were generated to determine the relevant phenotypes in a carotid artery wire injury model. RNA sequencing, assays for transposase-accessible chromatin using sequencing, computational prediction of complex structures, and coimmunoprecipitation were performed to elucidate the underlying molecular mechanisms. Adeno-associated virus-mediated Tax1bp3 gene delivery and nanoencapsulated-TAX1BP3 were employed to investigate the potential translational relevance.

resultsTAX1BP3 exhibited dynamic nucleocytoplasmic shuttling during phenotypic switching of VSMCs. TAX1BP3 is SUMOylated at K116, and its SUMOylation is essential for maintaining the nuclear localization of TAX1BP3. Deficiency of TAX1BP3 facilitated the transition from a contractile to a synthetic phenotype and aggravated neointima formation after vascular injury in mice. The integration of RNA sequencing and an assay for transposase-accessible chromatin using sequencing unveiled that TAX1BP3 primarily regulated the cell cycle progression and cell proliferation of VSMCs through YAP-TEAD transcription activity. The computational prediction of TAX1BP3/YAP1 complex structures and protein interaction-related experiments revealed that TAX1BP3 and TEAD1 compete for binding to YAP through its TEAD binding domain (BD) in a noncanonical PDZ manner. AAV-mediated Tax1bp3 gene delivery significantly attenuated postinjury neointima formation and the progression of atherosclerosis. Nanoencapsulated-TAX1BP3 administration effectively reduced VSMC phenotypic switching and neointimal hyperplasia.

conclusionsThese results demonstrate that SUMOylation of TAX1BP3 at K116 enables its nucleocytoplasmic shuttling during phenotypic switching of VSMCs. TAX1BP3 competitively interacts with the YAP-TEAD complex in a noncanonical PDZ manner and exerts its protective role in vascular neointimal hyperplasia primarily through the regulation of cell proliferation.

Indexed as

Carotid Artery InjuriesMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaSumoylationAnimalsCells, CulturedHumansHyperplasiaMaleMiceMice, Inbred C57BLMice, Knockoutarterial diseasescell proliferationPDZ domainsvascular injuriesvascular smooth muscle

Identifiers

PMID40955569

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