ArticleProceedings of the National Academy of Sciences of the United States of America2019
26S Proteasomes are rapidly activated by diverse hormones and physiological states that raise cAMP and cause Rpn6 phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- PKA-Mediated Proteasome Activation Protects Against Cardiac Remodeling and Heart Failure During Systolic Overload.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?Molecular neurobiology · 2025Review
- A Critical Assessment of Fasting to Promote Metabolic Health and Longevity.Endocrine reviews · 2025Review
- Article
- Muscle in Endocrinology: From Skeletal Muscle Hormone Regulation to Myokine Secretion and Its Implications in Endocrine-Metabolic Diseases.Journal of clinical medicine · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Activators of the 26S proteasome when protein degradation increases.Experimental & molecular medicine · 2025Review
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- Organoids in biliary research: insights into developmental signaling and applications in disease modeling.Frontiers in cell and developmental biology · 2025Review
- Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle.Journal of cachexia, sarcopenia and muscle · 2024Review
- Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.Cellular and molecular life sciences : CMLS · 2024Article
- Proteasome gene expression is controlled by coordinated functions of multiple transcription factors.The Journal of cell biology · 2024Article
- PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response.American journal of human genetics · 2024Article
- Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pharmacological agents that raise cAMP and activate protein kinase A (PKA) stimulate 26S proteasome activity, phosphorylation of subunit Rpn6, and intracellular degradation of misfolded proteins. We investigated whether a similar proteasome activation occurs in response to hormones and under various physiological conditions that raise cAMP. Treatment of mouse hepatocytes with glucagon, epinephrine, or forskolin stimulated Rpn6 phosphorylation and the 26S proteasomes' capacity to degrade ubiquitinated proteins and peptides. These agents promoted the selective degradation of short-lived proteins, which are misfolded and regulatory proteins, but not the bulk of cell proteins or lysosomal proteolysis. Proteasome activities and Rpn6 phosphorylation increased similarly in working hearts upon epinephrine treatment, in skeletal muscles of exercising humans, and in electrically stimulated rat muscles. In WT mouse kidney cells, but not in cells lacking PKA, treatment with antidiuretic hormone (vasopressin) stimulated within 5-minutes proteasomal activity, Rpn6 phosphorylation, and the selective degradation of short-lived cell proteins. In livers and muscles of mice fasted for 12-48 hours cAMP levels, Rpn6 phosphorylation, and proteasomal activities increased without any change in proteasomal content. Thus, in vivo cAMP-PKA-mediated proteasome activation is a common cellular response to diverse endocrine stimuli and rapidly enhances the capacity of target tissues to degrade regulatory and misfolded proteins (e.g., proteins damaged upon exercise). The increased destruction of preexistent regulatory proteins may help cells adapt their protein composition to new physiological conditions.
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