ArticleCellular signalling2015
UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- The toxicological impact of PET-MPs exposure on atherosclerosis: insights from network toxicology, molecular docking, and machine learning.Scientific reports · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- Nsun2 controls cardiac homeostasis and hypertrophic response by regulating PRKACA expression.Theranostics · 2025Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma.Scientific reports · 2024Article
- Protein Kinase A Is a Master Regulator of Physiological and Pathological Cardiac Hypertrophy.Circulation research · 2024Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2023Review
- Inhibition of phosphodiesterase 4D suppresses mTORC1 signaling and pancreatic cancer growth.JCI insight · 2023Article
- Regulation of cardiac function by cAMP nanodomains.Bioscience reports · 2023Review
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors.RSC advances · 2020Article
- Review
- Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches.Biochemical Society transactions · 2019Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- C1q-TNF-related protein-3 attenuates pressure overload-induced cardiac hypertrophy by suppressing the p38/CREB pathway and p38-induced ER stress.Cell death & disease · 2019Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypertrophy increases the risk of heart failure and arrhythmia. Prevention or reversal of the maladaptive hypertrophic phenotype has thus been proposed to treat heart failure. Chronic β-adrenergic receptor (β-AR) stimulation induces cardiomyocyte hypertrophy by elevating 3',5'-cyclic adenosine monophosphate (cAMP) levels and activating downstream effectors such protein kinase A (PKA). Conversely, hydrolysis of cAMP by phosphodiesterases (PDEs) spatiotemporally restricts cAMP signaling. Here, we demonstrate that PDE4, but not PDE3, is critical in regulating cardiomyocyte hypertrophy, and may represent a potential target for preventing maladaptive hypertrophy. We identify a sequence within the upstream conserved region 1 of PDE4D, termed UCR1C, as a novel activator of PDE4 long isoforms. UCR1C activates PDE4 in complex with A-kinase anchoring protein (AKAP)-Lbc resulting in decreased PKA signaling facilitated by AKAP-Lbc. Expression of UCR1C in cardiomyocytes inhibits hypertrophy in response to chronic β-AR stimulation. This effect is partially due to inhibition of nuclear PKA activity, which decreases phosphorylation of the transcription factor cAMP response element-binding protein (CREB). In conclusion, PDE4 activation by UCR1C attenuates cardiomyocyte hypertrophy by specifically inhibiting nuclear PKA activity.
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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.