ArticleNature communications2019
Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
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- Computational Systems Biology Approaches to Cellular Aging - Integrating Network Maps and Dynamical Models.Quantitative biology (Beijing, China) · 2025Article
- CHIP mediates glucagon action on hepatic glucose production via regulating Smad3 ubiquitination.Diabetes, obesity & metabolism · 2025Article
- Protein kinase A is a dependent factor and therapeutic target in mouse models of fibrous dysplasia.Nature communications · 2025Article
- USP24 upregulation stabilizes PKA-Cα to promote lipogenesis, inflammation, and fibrosis during MASH progression.Journal of biomedical science · 2025Article
- USP8 and Hsp70 regulate endoreplication by synergistically promoting Fzr deubiquitination and stabilization.Science advances · 2025Article
- Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.PLoS biology · 2025Article
- E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.The EMBO journal · 2025Article
- Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies.Movement disorders : official journal of the Movement Disorder Society · 2024Article
- Article
- Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA-protein interactions.Cellular and molecular life sciences : CMLS · 2024Article
- Glucose inhibits the inflammatory response in goose fatty liver by increasing the ubiquitination level of PKA.Journal of animal science · 2024Article
- Elucidating cellular interactome of chikungunya virus identifies host dependency factors.Virologica Sinica · 2023Article
- The MyD88 inhibitor, ST2825, induces cell cycle arrest and apoptosis by suppressing the activation of the NF‑κB/AKT1/p21 pathway in pancreatic cancer.Oncology reports · 2023Article
- Mislocalization of protein kinase A drives pathology in Cushing's syndrome.Cell reports · 2022Article
- Site-specific ubiquitination: Deconstructing the degradation tag.Current opinion in structural biology · 2022Review
- Brain metastases: It takes two factors for a primary cancer to metastasize to brain.Frontiers in oncology · 2022Article
- Pathophysiology of Primary Cilia: Signaling and Proteostasis Regulation.Frontiers in cell and developmental biology · 2022Review
- GPharmacological reviews · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
Activation of G-protein coupled receptors elevates cAMP levels promoting dissociation of protein kinase A (PKA) holoenzymes and release of catalytic subunits (PKAc). This results in PKAc-mediated phosphorylation of compartmentalized substrates that control central aspects of cell physiology. The mechanism of PKAc activation and signaling have been largely characterized. However, the modes of PKAc inactivation by regulated proteolysis were unknown. Here, we identify a regulatory mechanism that precisely tunes PKAc stability and downstream signaling. Following agonist stimulation, the recruitment of the chaperone-bound E3 ligase CHIP promotes ubiquitylation and proteolysis of PKAc, thus attenuating cAMP signaling. Genetic inactivation of CHIP or pharmacological inhibition of HSP70 enhances PKAc signaling and sustains hippocampal long-term potentiation. Interestingly, primary fibroblasts from autosomal recessive spinocerebellar ataxia 16 (SCAR16) patients carrying germline inactivating mutations of CHIP show a dramatic dysregulation of PKA signaling. This suggests the existence of a negative feedback mechanism for restricting hormonally controlled PKA activities.
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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.