ArticleProceedings of the National Academy of Sciences of the United States of America2020
Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 65 citations in OpenAlex.
- Ubiquitin receptor-mediated, ubiquitin-independent targeted protein degradation via 26Science advances · 2026Article
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- PINK1 and STUB1 pathway orchestrates peroxisomal selective autophagy by PEX13 depletion.Cell death and differentiation · 2026Article
- The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons.Nature communications · 2026Article
- Multilayer modulation of the proteasome: new strategies for neuroprotection.Frontiers in molecular neuroscience · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Discovery of Small-Molecule Ligands for the E3 Ligase STUB1/CHIP from a DNA-Encoded Library Screen.ACS medicinal chemistry letters · 2025Article
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- A ubiquitin-specific, proximity-based labeling approach for the identification of ubiquitin ligase substrates.Science advances · 2024Article
- Proteostasis perturbation of N-Myc leveraging HSP70 mediated protein turnover improves treatment of neuroendocrine prostate cancer.Nature communications · 2024Article
- Novel autophagy inducers by accelerating lysosomal clustering against Parkinson's disease.eLife · 2024Article
- Self-Aggregating Tau Fragments Recapitulate Pathologic Phenotypes and Neurotoxicity of Alzheimer's Disease in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung adenocarcinoma.iScience · 2023Article
- To Kill or to Be Killed: How Does the Battle between the UPS and Autophagy Maintain the Intracellular Homeostasis in Eukaryotes?International journal of molecular sciences · 2023Review
- Manipulating autophagic degradation in human diseases: from mechanisms to interventions.Life medicine · 2022Review
- Proteasome granule formation is regulated through mitochondrial respiration and kinase signaling.Journal of cell science · 2022Article
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- Review
- Evaluation of Immunoproteasome-Specific Proteolytic Activity Using Fluorogenic Peptide Substrates.Immune network · 2022Article
- Centrosomes grow aggresomes to clear waste.Nature cell biology · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 26S proteasome, a self-compartmentalized protease complex, plays a crucial role in protein quality control. Multiple levels of regulatory systems modulate proteasomal activity for substrate hydrolysis. However, the destruction mechanism of mammalian proteasomes is poorly understood. We found that inhibited proteasomes are sequestered into the insoluble aggresome via HDAC6- and dynein-mediated transport. These proteasomes colocalized with the autophagic receptor SQSTM1 and cleared through selective macroautophagy, linking aggresomal segregation to autophagic degradation. This proteaphagic pathway was counterbalanced with the recovery of proteasomal activity and was critical for reducing cellular proteasomal stress. Changes in associated proteins and polyubiquitylation on inhibited 26S proteasomes participated in the targeting mechanism to the aggresome and autophagosome. The STUB1 E3 Ub ligase specifically ubiquitylated purified human proteasomes in vitro, mainly via Lys63-linked chains. Genetic and chemical inhibition of STUB1 activity significantly impaired proteasome processing and reduced resistance to proteasomal stress. These data demonstrate that aggresomal sequestration is the crucial upstream event for proteasome quality control and overall protein homeostasis in mammals.
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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.