ArticleCirculation2025
Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration.
Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Hippo Pathway-YAP/TAZ Signaling: Molecular Mechanisms, Biological Function, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Isomucronulatol attenuates liver aging by inhibiting GSK-3β acetylation and promoting β-catenin accumulation.Journal of natural medicines · 2026Article
- Moderate downregulation of NDUFA13 promotes cardiomyocytes proliferation and heart regeneration through the glycolysis/c‑Myc/International journal of molecular medicine · 2026Article
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.Circulation · 2026Article
- TEAD-independent mechanisms of YAP function in cardiomyocyte cell cycle reentry.Life science alliance · 2026Article
- ROS-Mediated Cardiomyocyte Proliferation and Myocardial Regeneration: Mechanisms and Targeted Strategies for Ischemic Heart Disease.Journal of cardiovascular development and disease · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Targeting the Hippo Pathway for Cardiac Regeneration.Physiology (Bethesda, Md.) · 2025Review
- Restoration of SIRT3 Expression in Aged Mice Alleviates UUO-Induced Renal Fibrosis by Reducing GSK-3β Hyperacetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell type specificity of Hippo-YAP signaling in cardiac development and disease.Journal of molecular and cellular cardiology · 2025Review
- Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.Cell regeneration (London, England) · 2025Review
- Review
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Article
- Dysfunctional cardiomyocyte signalling and heart disease.Current opinion in cell biology · 2025Review
- Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration.Seminars in cell & developmental biology · 2025Review
- The effects of YAP/TAZ in cardiomyocytes: a scoping review.Molecular biology reports · 2025Article
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9 authors.
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Abstract
backgroundThe Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined.
methodsWe identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the protein-protein interactors by YAP immunoprecipitation followed by mass spectrometry, then validated the YAP interaction in neonatal rat ventricular myocytes. We examined colocalization of YAP and TUBA4A (tubulin α 4A) by superresolution imaging. Furthermore, we developed YAP-K265R and
resultsWe found that YAP is acetylated at K265 by CBP (CREB-binding protein)/P300 (E1A-binding protein P300) and is deacetylated by nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide/sirtuins axis in cardiomyocytes. After myocardial infarction, YAP acetylation is increased, which promotes YAP cytoplasmic localization. Compared with controls, mice that were genetically engineered to express a K265R mutation that prevents YAP K265 acetylation showed improved cardiac regenerative ability and increased YAP nuclear localization. Mechanistically, YAP acetylation facilitates its interaction with TUBA4A, a component of the microtubule network that sequesters acetylated YAP in the cytoplasm. After myocardial infarction, the microtubule network increased in cardiomyocytes, resulting in the accumulation of YAP in the cytoplasm.
conclusionsAfter myocardial infarction, decreased sirtuin activity enriches YAP acetylation at K265. The growing TUBA4A network sequesters acetylated YAP within the cytoplasm, which is detrimental to cardiac regeneration.
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