ArticleThe Journal of biological chemistry2014
Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 115 citations in OpenAlex.
- The SQSTM1 L341V Variant Associated With Sporadic ALS Promotes the Accumulation of Enlarged Ubiquitin-Positive SQSTM1 Bodies.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Interaction of CSN4 to DDB1 regulates its stability and function in DNA damage signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.Current issues in molecular biology · 2025Article
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- Article
- Interplay between autophagy and CncC regulates dendrite pruning inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Amino Acid-Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin-Proteasome System for Nutrient Acquisition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.PloS one · 2024Article
- The deubiquitinase Leon/USP5 interacts with Atg1/ULK1 and antagonizes autophagy.Cell death & disease · 2023Article
- Immortalized Alzheimer's Disease Astrocytes: Characterization of Their Proteolytic Systems.Molecular neurobiology · 2023Article
- PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.Cell & bioscience · 2023Article
- Proteasomal inhibition preferentially stimulates lysosome activity relative to autophagic flux in primary astrocytes.Autophagy · 2023Article
- Potential benefits of medium chain fatty acids in aging and neurodegenerative disease.Frontiers in aging neuroscience · 2023Review
- The contribution of proteasomal impairment to autophagy activation by C9orf72 poly-GA aggregates.Cellular and molecular life sciences : CMLS · 2022Article
- Transgenic Expression of Nrf2 Induces a Pro-Reductive Stress and Adaptive Cardiac Remodeling in the Mouse.Genes · 2022Article
- Reciprocal regulation of NRF2 by autophagy and ubiquitin-proteasome modulates vascular endothelial injury induced by copper oxide nanoparticles.Journal of nanobiotechnology · 2022Article
- The caspase-6-p62 axis modulates p62 droplets based autophagy in a dominant-negative manner.Cell death and differentiation · 2022Article
- Long noncoding RNA BCRP3 stimulates VPS34 and autophagy activities to promote protein homeostasis and cell survival.Journal of biomedical science · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. These pathways are interdependent, and dysfunction in either pathway causes accumulation of ubiquitin-positive aggregates, a hallmark of human pathological conditions. To elucidate in vivo compensatory action(s) against proteasomal dysfunction, we developed mice with reduced proteasome activity in their livers. The mutant mice exhibited severe liver damage, accompanied by formation of aggregates positive for ubiquitin and p62/Sqstm1, an adaptor protein for both selective autophagy and the anti-oxidative Keap1-Nrf2 pathway. These aggregates were selectively entrapped by autophagosomes, and pathological features of livers with impaired proteasome activity were exacerbated by simultaneous suppression of autophagy. In contrast, concomitant loss of p62/Sqstm1 had no apparent effect on the liver pathology though p62/Sqstm1 was indispensable for the aggregates formation. Furthermore, defective proteasome function led to transcriptional activation of the Nrf2, which served as a physiological adaptation. Our in vivo data suggest that cells contain networks of cellular defense mechanisms against defective proteostasis.
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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.