ArticleCell death & disease2016
Tankyrase inhibition aggravates kidney injury in the absence of CD2AP.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- A TGF-β1/LEF1/β-catenin/JLP network motif regulates autophagy and tubule injury in renal fibrosis.JCI insight · 2026Article
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis.Open medicine (Warsaw, Poland) · 2024Article
- Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish.Journal of developmental biology · 2023Review
- An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.Biomolecules · 2022Article
- Review
- Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex.International journal of molecular sciences · 2021Article
- Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice.International journal of obesity (2005) · 2020Article
- CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer: An Integrated Analysis.Frontiers in molecular biosciences · 2020Article
- The role of CD2AP in the Pathogenesis of Alzheimer's Disease.Aging and disease · 2019Review
- Novel insight into the function of tankyrase.Oncology letters · 2018Review
- Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis.Scientific reports · 2017Article
- Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/Evidence-based complementary and alternative medicine : eCAM · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Inappropriate activation of the Wnt/β-catenin pathway has been indicated in podocyte dysfunction and injury, and shown to contribute to the development and progression of nephropathy. Tankyrases, multifunctional poly(ADP-ribose) polymerase (PARP) superfamily members with features of both signaling and cytoskeletal proteins, antagonize Wnt/β-catenin signaling. We found that tankyrases interact with CD2-associated protein (CD2AP), a protein essential for kidney ultrafiltration as CD2AP-knockout (CD2AP-/-) mice die of kidney failure at the age of 6-7 weeks. We further observed that tankyrase-mediated total poly-(ADP-ribosyl)ation (PARylation), a post-translational modification implicated in kidney injury, was increased in mouse kidneys and cultured podocytes in the absence of CD2AP. The data revealed increased activity of β-catenin, and upregulation of lymphoid enhancer factor 1 (LEF1) (mediator of Wnt/β-catenin pathway) and fibronectin (downstream target of Wnt/β-catenin) in CD2AP-/- podocytes. Total PARylation and active β-catenin were reduced in CD2AP-/- podocytes by tankyrase inhibitor XAV939 treatment. However, instead of ameliorating podocyte injury, XAV939 further upregulated LEF1, failed to downregulate fibronectin and induced plasminogen activator inhibitor-1 (PAI-1) that associates with podocyte injury. In zebrafish, administration of XAV939 to CD2AP-depleted larvae aggravated kidney injury and increased mortality. Collectively, the data reveal sustained activation of the Wnt/β-catenin pathway in CD2AP-/- podocytes, contributing to podocyte injury. However, we observed that inhibition of the PARylation activity of tankyrases in the absence of CD2AP was deleterious to kidney function. This indicates that balance of the PARylation activity of tankyrases, maintained by CD2AP, is essential for normal kidney function. Furthermore, the data reveal that careful contemplation is required when targeting Wnt/β-catenin pathway to treat proteinuric kidney diseases associated with impaired CD2AP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.