ArticleNature communications2020
CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Domain-dependent uncoupling of the co-chaperone and E3 ubiquitin ligase CHIP underlies heterogeneity in spinocerebellar ataxia 48.The Journal of biological chemistry · 2026Article
- Crystal structures reveal phosphorylation-dependent disruption of the heat shock protein 70-CHIP interface: A compensatory G132N variant restores binding affinity.Cell stress & chaperones · 2026Article
- Single-Cell RNA Sequencing Reveals Impaired CHIP-Mediated Heat Stress Response in SCA3 Pathogenesis.Molecular neurobiology · 2026Article
- Stub1 Acetylation by CBP/p300 Attenuates Chronic Hypoxic-Driven Pulmonary Hypertension by Suppressing HIF-2α.American journal of respiratory cell and molecular biology · 2025Article
- Will Stub1 Be the Next Target for Pulmonary Hypertension Therapy Development?American journal of respiratory cell and molecular biology · 2025Article
- CHIP and aging: a key regulator of proteostasis and cellular senescence.Biogerontology · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation.Scientific reports · 2025Article
- E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.The EMBO journal · 2025Article
- Activators of the 26S proteasome when protein degradation increases.Experimental & molecular medicine · 2025Review
- 5-HTJournal of advanced research · 2025Article
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.Cellular and molecular life sciences : CMLS · 2024Article
- STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-β-catenin axis.Communications biology · 2024Article
- Targeting the Lysosomal Degradation of Rab22a-NeoF1 Fusion Protein for Osteosarcoma Lung Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus of Hsc70-interacting protein (CHIP) is an important regulator of proteostasis in many cells, having E3-ligase and chaperone functions and often directing damaged proteins towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation. Here we report that CHIP-mediated protein turnover is markedly post-translationally enhanced by direct protein kinase G (PKG) phosphorylation at S20 (mouse, S19 human). This increases CHIP binding affinity to Hsc70, CHIP protein half-life, and consequent clearance of stress-induced ubiquitinated-insoluble proteins. PKG-mediated CHIP-pS20 or expressing CHIP-S20E (phosphomimetic) reduces ischemic proteo- and cytotoxicity, whereas a phospho-silenced CHIP-S20A amplifies both. In vivo, depressing PKG activity lowers CHIP-S20 phosphorylation and protein, exacerbating proteotoxicity and heart dysfunction after ischemic injury. CHIP-S20E knock-in mice better clear ubiquitinated proteins and are cardio-protected. PKG activation provides post-translational enhancement of protein quality control via CHIP.
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Registered trials
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.