ArticleJournal of molecular biology2012
DnaJA1 antagonizes constitutive Hsp70-mediated stabilization of tau.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- DNAJB6a deficiency induces tau pathology through IRE1α-Xbp1-induced mitochondria dysfunction.Zoological research · 2026Article
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- A J-domain protein enhances memory by promoting physiological amyloid formation inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mitochondrial subtypes in renal ischemia reperfusion injury guide delayed graft function and Long-Term graft prediction.Scientific reports · 2025Article
- Chaperone-mediated heterotypic phase separation regulates liquid-to-solid phase transitions of tau into amyloid fibrils.Science advances · 2025Article
- Selenoprotein W modulates tau homeostasis in an Alzheimer's disease mouse model.Communications biology · 2024Article
- DNAJB8 oligomerization is mediated by an aromatic-rich motif that is dispensable for substrate activity.Structure (London, England : 1993) · 2024Article
- Novel insights into the post-translational modifications of Ydj1/DNAJA1 co-chaperones.Cell stress & chaperones · 2024Review
- DnaJs are enriched in tau regulators.International journal of biological macromolecules · 2023Article
- Genome-Wide Association Analysis of Heat Tolerance in FInternational journal of molecular sciences · 2023Article
- The HSP40 family chaperone isoform DNAJB6b prevents neuronal cells from tau aggregation.BMC biology · 2023Article
- Identification of gene networks mediating regional resistance to tauopathy in late-onset Alzheimer's disease.PLoS genetics · 2023Article
- DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen.Cell death discovery · 2022Article
- The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity.EMBO molecular medicine · 2022Article
- Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau.The Journal of biological chemistry · 2022Article
- Hsp40s play distinct roles during the initial stages of apolipoprotein B biogenesis.Molecular biology of the cell · 2022Article
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- Article
- Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Finding associations in a heterogeneous setting: statistical test for aberration enrichment.Genome medicine · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Tau aggregation and amyloidogenesis are common hallmarks for neurodegenerative disorders called tauopathies. The molecular chaperone network constitutes the cellular defense against insults such as tau aggregation. However, chaperone effects on tau are dichotomous. Loss of tau's microtubule-binding activity facilitates an inappropriate chaperone interaction that promotes an amyloidogenic tau conformation. Conversely, other chaperones are capable of promoting tau clearance. Here, we demonstrate that a critical contributor to tau triage is the DnaJ-binding domain of Hsp70 proteins. In particular, over-expression of the constitutive DnaJ, DnaJA1, mediated tau clearance, while knockdown facilitated tau accumulation. This clearance was not specific to distinct pathogenic tau species. The activity of DnaJA1 was attenuated by concomitant increases in Hsp70. Tau reductions facilitated by DnaJA1 were dependent on the integrity of lysines known to be poly-ubiquitinated in human Alzheimer's brain. In vivo, DnaJA1 and tau levels were inversely correlated. The effects of DnaJA1 were partially specific: DnaJA1 reduced the levels of a polyQ protein but had no significant effect on α-synuclein levels. These data suggest that DnaJA1 triages all tau species for ubiquitin-dependent clearance mechanisms. Moreover, the levels of DnaJA1 and Hsp70 seem to play against each other with regard to tau: as DnaJA1 levels increase, tau levels are reduced, but this can be prevented if Hsp70 levels are simultaneously induced. Thus, the DnaJ repertoire possibly represents a powerful set of genetic modifiers for tau pathogenesis. Further investigations could provide new insights about triage decisions that facilitate or prevent amyloidogenesis of tau and other proteins associated with neurodegenerative disease.
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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.