ArticleThe Biochemical journal2006
Up-regulation of the clusterin gene after proteotoxic stress: implication of HSF1-HSF2 heterocomplexes.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 125 citations in OpenAlex.
- Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen.Cancer medicine · 2013Trial
- Clusterin in Head and Neck Squamous Cell Carcinoma: Diagnostic, Prognostic, and Therapeutic Implications.Current oncology reports · 2026Review
- Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Clusterin: a double-edged sword in cancer and neurological disorders.EXCLI journal · 2024Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations.ACS central science · 2023Article
- Heat Shock Transcription Factor 2 Is Significantly Involved in Neurodegenerative Diseases, Inflammatory Bowel Disease, Cancer, Male Infertility, and Fetal Alcohol Spectrum Disorder: The Novel Mechanisms of Several Severe Diseases.International journal of molecular sciences · 2022Review
- BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling.Nature communications · 2022Article
- Proteasome regulators in pancreatic cancer.World journal of gastrointestinal oncology · 2022Review
- The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body.Oxidative medicine and cellular longevity · 2022Review
- PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated Microgravity.Frontiers in cell and developmental biology · 2022Article
- Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses.Communications biology · 2021Article
- Effects of radiofrequency field exposure on proteotoxic-induced and heat-induced HSF1 response in live cells using the bioluminescence resonance energy transfer technique.Cell stress & chaperones · 2021Article
- Quantitative and multiplexed chemical-genetic phenotyping in mammalian cells with QMAP-Seq.Nature communications · 2020Article
- The Multiple Roles and Therapeutic Potential of Molecular Chaperones in Prostate Cancer.Cancers · 2019Review
- Increased clusterin levels after myocardial infarction is due to a defect in protein degradation systems activity.Cell death & disease · 2019Article
- Clusterin as a potential marker of brain ischemia-reperfusion injury in patients undergoing carotid endarterectomy.Upsala journal of medical sciences · 2019Article
- Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes.Toxicology research · 2019Article
- Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies.Frontiers in neuroscience · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clusterin is a secreted protein chaperone up-regulated in several pathologies, including cancer and neurodegenerative diseases. The present study shows that accumulation of aberrant proteins, caused by the proteasome inhibitor MG132 or the incorporation of the amino acid analogue AZC (L-azetidine-2-carboxylic acid), increased both clusterin protein and mRNA levels in the human glial cell line U-251 MG. Consistently, MG132 treatment was capable of stimulating a 1.3 kb clusterin gene promoter. Promoter deletion and mutation studies revealed a critical MG132-responsive region between -218 and -106 bp, which contains a particular heat-shock element, named CLE for 'clusterin element'. Gel mobility-shift assays demonstrated that MG132 and AZC treatments induced the formation of a protein complex that bound to CLE. As shown by supershift and chromatin-immunoprecipitation experiments, CLE is bound by HSF1 (heat-shock factor 1) and HSF2 upon proteasome inhibition. Furthermore, co-immunoprecipitation assays indicated that these two transcription factors interact. Gel-filtration analyses revealed that the HSF1-HSF2 heterocomplexes bound to CLE after proteasome inhibition have the same apparent mass as HSF1 homotrimers after heat shock, suggesting that HSF1 and HSF2 could heterotrimerize. Therefore these studies indicate that the clusterin is a good candidate to be part of a cellular defence mechanism against neurodegenerative diseases associated with misfolded protein accumulation or decrease in proteasome activity.
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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.