ArticleThe EMBO journal2015
Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 128 citations in OpenAlex.
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- P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Multi-omics network reconstruction with collaborative graphical lasso.Bioinformatics (Oxford, England) · 2026Article
- Interplay between proteostasis pathways and innate immune responses inInfection and immunity · 2026Review
- A mouse model of cardiac immunoglobulin light chain amyloidosis reveals insights into tissue accumulation and toxicity of amyloid fibrils.Nature communications · 2025Article
- The dynamics of prion spreading is governed by the interplay between the non-linearities of tissue response and replication kinetics.iScience · 2024Article
- Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach.Cells · 2024Review
- Factors affecting protein recovery during Hsp40 affinity profiling.Analytical and bioanalytical chemistry · 2024Article
- The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.Journal of molecular biology · 2024Review
- Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- ATM-mediated co-chaperone DNAJB11 phosphorylation facilitates α-synuclein folding upon DNA double-stranded breaks.NAR molecular medicine · 2024Article
- Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons.Cell reports · 2024Article
- Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model.Blood advances · 2023Article
- Endoplasmic Reticulum Stress-Regulated Chaperones as a Serum Biomarker Panel for Parkinson's Disease.Molecular neurobiology · 2023Article
- Extracellular chaperone networks and the export of J-domain proteins.The Journal of biological chemistry · 2023Review
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Safety and Efficacy of Subcutaneous Daratumumab in Systemic AL Amyloidosis.Therapeutics and clinical risk management · 2023Review
- Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.The Journal of biological chemistry · 2022Article
- Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications.International journal of molecular sciences · 2022Review
- Exosomal DNAJB11 promotes the development of pancreatic cancer by modulating the EGFR/MAPK pathway.Cellular & molecular biology letters · 2022Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The Unfolded Protein Response (UPR) indirectly regulates extracellular proteostasis through transcriptional remodeling of endoplasmic reticulum (ER) proteostasis pathways. This remodeling attenuates secretion of misfolded, aggregation-prone proteins during ER stress. Through these activities, the UPR has a critical role in preventing the extracellular protein aggregation associated with numerous human diseases. Here, we demonstrate that UPR activation also directly influences extracellular proteostasis through the upregulation and secretion of the ER HSP40 ERdj3/DNAJB11. Secreted ERdj3 binds misfolded proteins in the extracellular space, substoichiometrically inhibits protein aggregation, and attenuates proteotoxicity of disease-associated toxic prion protein. Moreover, ERdj3 can co-secrete with destabilized, aggregation-prone proteins in a stable complex under conditions where ER chaperoning capacity is overwhelmed, preemptively providing extracellular chaperoning of proteotoxic misfolded proteins that evade ER quality control. This regulated co-secretion of ERdj3 with misfolded clients directly links ER and extracellular proteostasis during conditions of ER stress. ERdj3 is, to our knowledge, the first metazoan chaperone whose secretion into the extracellular space is regulated by the UPR, revealing a new mechanism by which UPR activation regulates extracellular 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.