| 2003 |
Tpr2 (DNAJC7) contains two TPR domains that bind Hsp70 and Hsp90 simultaneously, and a J domain that stimulates Hsp70 ATPase activity and polypeptide binding. Unlike other co-chaperones, Tpr2 induces ATP-independent dissociation of Hsp90 (but not Hsp70) from chaperone-substrate complexes, mediating retrograde transfer of substrates from Hsp90 back onto Hsp70. Excess Tpr2 inhibits Hsp90-dependent folding of the glucocorticoid receptor (GR) in cell lysates. |
In vitro biochemical assays (ATPase stimulation, polypeptide binding), cell lysate GR folding assays, domain-binding studies, overexpression/knockdown in vivo |
The EMBO journal |
High |
12853476
|
| 2008 |
Tpr2 (DNAJC7) associates with Hsp90 and Hsp70 complexes that also contain the progesterone receptor (PR); it can bind Hsp70 and Hsp90 simultaneously, but unlike Hop, its binding to Hsp70 in the presence of Hsp90 is ATP-dependent. Tpr2 cannot replace Hop in Hsp90 chaperoning in vitro or in vivo. Tpr2 replaces type I and II J proteins in Hsp90-dependent chaperoning of the PR and Chk1 kinase and promotes accumulation of Hsp70 in PR heterocomplexes in the presence of Hsp90. |
Immunoprecipitation, pulldown, in vitro and in vivo chaperoning assays, knockdown/overexpression in HeLa cells |
Biochemistry |
High |
18620420
|
| 2001 |
Tpr2 (DNAJC7) binds Rad9, Rad1, and Hus1 (checkpoint clamp proteins) through its N-terminal TPR region. The J domain of Tpr2 negatively regulates its interaction with Rad9: deletion of the J domain or mutation of the conserved HPD motif greatly enhances Tpr2-Rad9 binding. Following heat-shock or UV treatment, Rad9 transiently dissociates from Tpr2 in a J-domain-dependent manner. The J domain also modulates the cellular localization of both Tpr2 and Rad9. |
Yeast two-hybrid screening, in vivo and in vitro binding assays, J-domain point mutation (HPD motif), cellular localization analysis |
Biochemical and biophysical research communications |
Medium |
11573955
|
| 2012 |
DnaJC7/TPR2 binds p53 through its central DNA-binding domain (identified by yeast two-hybrid), confirmed by co-immunoprecipitation in mammalian cells. DnaJC7 enhances p53-dependent transcriptional and growth-suppressive activity, extends p53 half-life, and reduces the amount of p53/MDM2 complex, suggesting DnaJC7 dissociates MDM2 from p53 to stabilize p53. |
Yeast two-hybrid screening, co-immunoprecipitation, luciferase reporter assay, colony formation assay, pulse-chase/half-life analysis |
Biochemical and biophysical research communications |
Medium |
23261415
|
| 2014 |
CCRP/DNAJC7 interacts with HSP70 (co-immunoprecipitation in HepG2 cells) and retains nuclear receptor CAR in the cytoplasm. DNAJC7 is ubiquitinated and degraded by the proteasome upon CAR activation; this ubiquitination of DNAJC7 (but not CAR itself) is increased by TCPOBOP in the presence of MG132. HSP70 induction by heat shock also increases cytoplasmic CAR levels and attenuates CAR transcriptional activation, phenocopying proteasome inhibition. |
Co-immunoprecipitation, proteasome inhibitor (MG132) treatment, ubiquitination assay, luciferase reporter assay, heat shock experiments in HepG2 cells |
PloS one |
Medium |
24789201
|
| 2014 |
CCRP/DNAJC7 knockout mice show increased nuclear CAR accumulation after phenobarbital treatment but paradoxically attenuated Cyp2b10 gene activation. ChIP assays reveal that DNAJC7 is required for phenobarbital-induced de-methylation of H3K27 on the Cyp2b10 promoter and for RNA polymerase II recruitment, but not for CAR/RXRα binding to the promoter. DNAJC7 KO males also develop steatotic livers and altered cholesterol levels upon fasting. |
Knockout mouse model, ChIP assays (H3K27 methylation, RNA Pol II, CAR/RXRα), immunoblotting, gene expression analysis |
PloS one |
High |
25542016
|
| 2016 |
Mass spectrometric and pulldown analysis identified DNAJC7 as a substrate of cytosolic carboxypeptidase 6 (CCP6). When CCP6 is reduced (as in RCC), DNAJC7 accumulates in a polyglutamylated form (polyE-DNAJC7) detectable in serum. |
Mass spectrometry, pulldown assay, immunohistochemistry, Western blot, electrochemiluminescence immunoassay |
Oncotarget |
Medium |
26993597
|
| 2021 |
DnaJC7 binds preferentially to natively folded wild-type tau (not aggregated conformers) using a single TPR domain that recognizes a β-turn structural element containing the 275VQIINK280 amyloid motif. Disease-associated tau mutants that disrupt this β-turn reduce DnaJC7 binding affinity. DnaJC7 efficiently suppresses tau aggregation in vitro and in cells. |
In vitro aggregation assays, binding affinity measurements, domain mapping (single TPR domain), peptide competition assays, cell-based aggregation assays |
Nature communications |
High |
34504072
|
| 2023 |
DnaJC7 co-purifies with insoluble tau and colocalizes with intracellular tau aggregates. Knockout of DnaJC7 (but not other JDPs) specifically decreases aggregate clearance and increases intracellular tau seeding. This protective activity depends on the ability of the DnaJC7 J domain to stimulate Hsp70 ATPase activity; J-domain mutations blocking Hsp70 interaction abolish protection. Disease-associated mutations in both the J domain and the substrate-binding site of DnaJC7 also abolish protective activity. |
Proteomics (co-purification with insoluble tau), CRISPR knockout of all JDPs individually, tau seeding assay, co-localization imaging, J-domain mutagenesis (HPD motif and ALS variants) |
eLife |
High |
37387473
|
| 2022 |
DnaJC7 acts as a bridge between Hsp70 and viral Hexon protein: the J domain of DnaJC7 is required for inhibiting FAdV-4 replication, and DnaJC7 mediates the indirect interaction between Hsp70 and Hexon. Hsp70 subsequently suppresses Hexon through the autophagy pathway to restrict viral replication. |
LC-MS/MS protein interaction screen, Co-IP, domain deletion analysis (J domain of DnaJC7, NBD of Hsp70), overexpression and autophagy inhibitor (chloroquine) experiments |
Journal of virology |
Medium |
35852354
|
| 2025 |
DNAJC7 knockdown impairs disassembly of TDP-43 condensates following arsenite-induced stress, while DNAJC7 overexpression suppresses assembly and promotes disassembly of arsenite-induced TDP-43 condensates. In a zebrafish ALS model, dnajc7 knockdown increases TDP-43 aggregation in motor neurons and reduces survival. |
Cell-based TDP-43 condensate assay with arsenite stress, DNAJC7 KD and OE, zebrafish dnajc7 morpholino knockdown, immunohistochemistry, RNA sequencing |
Acta neuropathologica |
Medium |
40802071
|
| 2026 |
The ALS-associated E425K mutation in the DNAJC7 J domain does not alter protein structure (confirmed by NMR) but specifically disrupts J-domain–Hsp70 interaction, uncoupling DNAJC7 from Hsp70 activation. A second Hsp70-binding interface exists in the TPR domains (binding the C-terminal EEVD motif of Hsp70), which is preserved in E425K but cannot compensate for loss of J-domain function. The TPR domains of DNAJC7 directly bind TDP-43 and prevent its aggregation (holdase activity retained in E425K), but the mutant fails to support client transfer to Hsp70 and subsequent Hsp70-mediated substrate refolding. |
NMR spectroscopy (structural and interaction analysis), in vitro binding assays, Hsp70 ATPase activation assay, TDP-43 aggregation assay |
The FEBS journal |
High |
41531269
|
| 2024 |
The DNAJC7 interactome in human motor neurons (iPSC-derived) is enriched for RNA-binding proteins (RBPs) and stress-response chaperones (mass spectrometry). The ALS-associated R156X loss-of-function mutation causes increased insolubility of client RBP HNRNPU and associated RNA metabolism alterations. DNAJC7 haploinsufficiency renders motor neurons susceptible to proteotoxic stress and cell death through an ablated HSF1 stress-response pathway; exogenous HSF1 expression rescues sensitivity to proteotoxic stress in DNAJC7-mutant motor neurons. |
Mass spectrometry interactome, iPSC-derived motor neurons with ALS mutation (R156X), protein solubility fractionation, HSF1 rescue experiment, RNA sequencing |
bioRxivpreprint |
Medium |
39651147
|
| 2025 |
USP19 deubiquitinates DnaJC7, increasing its protein stability. Upregulation of both USP19 and DnaJC7 disrupts the p53-MDM2 interaction; knockdown of USP19 and DnaJC7 decreases p53 expression following cisplatin treatment, indicating that the USP19-DnaJC7 axis stabilizes p53. |
Co-immunoprecipitation (USP19-DnaJC7 interaction), deubiquitination assay, knockdown experiments, p53 stability and MDM2 interaction assays in cisplatin-treated cells |
Cells |
Medium |
42193933
|
| 2026 |
DNAJC7 is a potent suppressor of polyglutamine (polyQ) aggregation, identified in a genome-wide CRISPRi screen of all chaperones. Physical interaction between DNAJC7 and polyQ-expanded protein was established. DNAJC7 knockdown specifically increased polyQ aggregation, while overexpressed DNAJC7 colocalized with both polyQ and polyG aggregates and reduced their aggregation. Direct knockdown of DNAJC7 did not affect polyG aggregation in the baseline model (negative result for polyG). |
FRET-based aggregation reporter, CRISPRi screen (all chaperones), KD validation, overexpression colocalization in human cells |
The Journal of biological chemistry |
Medium |
41708002
|