Cited by 122Ubiquitin and proteasome pathwaysHeat shock proteins researchAutophagy in Disease and Therapy

26S Proteasomes are rapidly activated by diverse hormones and physiological states that raise cAMP and cause Rpn6 phosphorylation

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VerPlank, Jordan J. S., Lokireddy, Sudarsanareddy, Zhao, Jinghui, Goldberg, Alfred L.·2019·Proceedings of the National Academy of Sciences

Abstract

Significance: Most studies of proteolysis by the ubiquitin-proteasome pathway have focused on the regulation by ubiquitination. However, we showed that pharmacological agents that raise cAMP and activate protein kinase A by phosphorylating a proteasome subunit enhance proteasome activity and the cell’s capacity to selectively degrade misfolded and regulatory proteins. We investigated whether similar adaptations occur in physiological conditions where cAMP rises. Proteasome activity increases by this mechanism in human muscles following intense exercise, in mouse muscles and liver after a brief fast, in hepatocytes after epinephrine or glucagon, and renal collecting duct cells within 5 minutes of antidiuretic hormone. Thus, hormones and conditions that raise cAMP rapidly enhance proteasome activity and the cells’ capacity to eliminate damaged and preexistent regulatory proteins.

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Crossref · 10.1073/pnas.1809254116

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39 of 39 references verified0 citation errors · 0 not checkable

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  • Absence of nutrients induces PKA-mediated phosphorylation of the proteasome subunit Rpn6, enhancing proteasomal degradation.

    “Consistently, the absence of nutrients induces PKA-mediated phosphorylation of the proteasome subunits Rpn6, enhancing proteasomal degradation59.”

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Authors
VerPlank, J. J. S., Lokireddy, S., Zhao, J., & Goldberg, A. L.
Affiliations
Harvard University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2019-02-19
Volume
116
Issue
10
Pages
4228-4237
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2917485599
Cited by
122
References
39
Citations by year
2026: 6 · 2025: 14 · 2024: 17 · 2023: 14 · 2022: 16 · 2021: 25 · 2020: 21 · 2019: 9
FWCI
5.88
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Institute of General Medical Sciences (R01 GM051923-20, F32 GM128322)
  • Cure Alzheimer's Fund
  • Muscular Dystrophy Association (MDA-419143)
  • Genentech
  • Project ALS
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
cyclic AMP, protein kinase A, glucagon, epinephrine, forskolin, vasopressin, misfolded protein degradation, ubiquitinated proteins, fasting, physical activity, muscle electrical stimulation, heart, hepatocytes, kidney cells
MeSH terms
Animals, Disease Models, Animal, Epinephrine, Colforsin, Glucagon, Humans, Kidney, Male, Phosphorylation, 8-Bromo Cyclic Adenosine Monophosphate, Rats, Sprague-Dawley, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases, Muscle, Skeletal, Hepatocytes, Proteasome Endopeptidase Complex, Mice, Rats, Ubiquitinated Proteins, Proteostasis Deficiencies, Proteolysis

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