Affinage

DNAJB1

DnaJ homolog subfamily B member 1 · UniProt P25685

Length
340 aa
Mass
38.0 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAJB1 (Hsp40/Hdj1) is a heat-inducible type II J-domain co-chaperone that stimulates Hsp70-dependent protein refolding and quality control in both cytoplasm and nucleus, accelerating Hsp70-mediated reactivation of heat-denatured substrates (PMID:9407119) and acting upstream of the Hsp90 chaperoning pathway by binding client proteins such as the progesterone receptor as the first ATP-independent step in maturation (PMID:11809754). Its transcription is driven by HSF1 binding to heat shock elements in its promoter (PMID:8975727, PMID:9545528). DNAJB1 governs aggregation-prone clients through distinct mechanisms: it phase-separates into ubiquitin-rich nuclear bodies and stress granules via its G/F-rich region, co-condensing with FUS to stabilize the liquid phase against amyloid conversion (PMID:33229560), and it carries a dedicated HTT-binding motif (His244) in its CTD-I/CTD-II hinge that is essential for disaggregation of huntingtin fibrils by the Hsc70/DNAJB1/Apg2 complex (PMID:35948542). Through Hsp70 partnership it also restrains nuclear receptor activity, recognizing the androgen receptor N-terminal FQNLF motif to maintain an inactive conformation and destabilize AR splice variants (PMID:31395886, PMID:29764864). DNAJB1 additionally functions as a regulatory node coupling chaperone activity to signaling and turnover, stabilizing MDM2 to dampen p53 activity (PMID:24361594), driving ubiquitin-dependent degradation of PDCD5 (PMID:25444898) and MIG6 (PMID:26239118), and suppressing MDA5 multimerization to limit type I interferon induction (PMID:29069650). Clinically, an in-frame chromosome-19 deletion fuses DNAJB1 exon 1 to the PKA catalytic subunit PRKACA, generating an oncogenic fusion kinase that is sufficient to drive fibrolamellar hepatocellular carcinoma in mice and to which tumors remain addicted (PMID:24578576, PMID:29162699, PMID:28923495, PMID:36302174).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established DNAJB1 as a functional Hsp70 co-chaperone, answering whether human Hsp40 actively assists refolding rather than acting alone.

    Evidence Co-transfection in hamster fibroblasts with compartment-targeted luciferase reactivation assays

    PMID:9407119

    Open questions at the time
    • Did not define the molecular step (ATPase stimulation) by which Hsp40 aids Hsp70
    • Client range beyond luciferase untested
  2. 2001 High

    Placed DNAJB1 at the entry point of receptor chaperoning by showing it binds client before Hsp70 in the Hsp90 pathway.

    Evidence Purified-protein reconstitution with equilibrium binding and hormone-binding activity assays on progesterone receptor

    PMID:11809754

    Open questions at the time
    • In vitro only; cellular relevance of the ordered handoff not shown
    • Structural basis of PR recognition undefined
  3. 2014 High

    Identified the DNAJB1-PRKACA fusion as a recurrent genetic lesion in fibrolamellar HCC, connecting the gene to a defined human cancer.

    Evidence RNA-seq, reciprocal IP, Western blot and kinase assay in tumor tissue (15/15 tumors)

    PMID:24578576

    Open questions at the time
    • Did not prove the fusion is causal for tumorigenesis
    • Role of the DNAJB1 portion in kinase dysregulation unresolved
  4. 2013 Medium

    Connected chaperone function to the p53 axis by showing DNAJB1 stabilizes MDM2 and tunes p53 pathway output.

    Evidence Yeast two-hybrid, Co-IP, in vitro binding, ubiquitination and cell growth assays

    PMID:24361594

    Open questions at the time
    • Single lab; reciprocal validation of the MDM2 interaction limited
    • Whether stabilization requires J-domain/Hsp70 activity unknown
  5. 2016 Medium

    Showed DNAJB1 participates in viral and innate-immune processes, both aiding influenza vRNP nuclear import and being co-opted by viral proteins.

    Evidence Yeast two-hybrid and Co-IP with domain mapping, RNAi, and nuclear import/replication assays (NP, M2, P58IPK)

    PMID:21204021 PMID:21698289 PMID:26750153

    Open questions at the time
    • Mechanisms inferred from interaction plus functional readout, partly indirect
    • Single-lab findings without structural validation
  6. 2017 High

    Demonstrated the DNAJB1-PRKACA fusion is sufficient to drive FL-HCC-like liver tumors in vivo, establishing causality.

    Evidence CRISPR-Cas9 and transposon somatic gene transfer in mice, with Co-IP for beta-catenin

    PMID:28923495 PMID:29162699

    Open questions at the time
    • Did not define how the DNAJB1 moiety alters PKA signaling biochemically
    • Cell-of-origin and full downstream program incompletely mapped
  7. 2017 Medium

    Defined a role in antiviral signaling by showing DNAJB1 suppresses MDA5 multimerization to restrain type I interferon induction.

    Evidence Yeast two-hybrid, Co-IP, IFN reporter assay, siRNA knockdown, co-localization in stress granules

    PMID:29069650

    Open questions at the time
    • Single lab; no structural account of how multimer formation is blocked
    • Dependence on Hsp70 partnership untested
  8. 2020 High

    Revealed that DNAJB1 phase-separates via its G/F region and co-condenses with FUS to suppress amyloid conversion, defining a condensate-based chaperone mode.

    Evidence Live-cell imaging, in vitro phase separation, G/F-region mutagenesis, domain-swap and FUS aggregation assays

    PMID:33229560

    Open questions at the time
    • In-cell consequences for endogenous FUS function not fully resolved
    • Relationship between condensate role and canonical Hsp70 cycle unclear
  9. 2022 High

    Mapped a specific HTT-binding motif (H244) required for huntingtin fibril disaggregation, distinguishing substrate-specific recognition from general chaperone activity.

    Evidence In vitro disaggregation/suppression assays, H244A mutagenesis, HEK293 aggregation assay, binding studies

    PMID:35948542

    Open questions at the time
    • Whether the HBM engages other PRD-containing substrates untested
    • High-resolution structure of the DNAJB1-HTT interface not determined
  10. 2023 Medium

    Established oncogenic addiction to the fusion kinase by showing continued expression is required for FL-HCC tumor cell survival.

    Evidence Inducible shRNA tiling the fusion junction in patient-derived xenografts in vitro and in vivo

    PMID:36302174

    Open questions at the time
    • Did not identify the essential downstream effectors of the fusion
    • Single-lab PDX system

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DNAJB1's distinct activities—J-domain Hsp70 stimulation, G/F-driven phase separation, motif-specific substrate recognition, and its ubiquitin-pathway interactions—are integrated and whether the DNAJB1 portion of the oncogenic fusion contributes a chaperone-related function remain unresolved.
  • No structural model of how the fusion DNAJB1 domain reshapes PKA regulation
  • Mechanistic link between condensate chaperoning and substrate turnover roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 1 R-HSA-8953854 Metabolism of RNA 1
Partners
CTNNB1FUSHSPA1AIFIH1MDM2MIG6PDCD5PRKACA
Complex memberships
Hsc70/DNAJB1/Apg2 disaggregase complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 A ~400-kilobase deletion on chromosome 19 fuses DNAJB1 exon 1 in-frame with PRKACA (catalytic subunit of PKA), generating a chimeric DNAJB1-PRKACA protein detected by immunoprecipitation and Western blot in fibrolamellar hepatocellular carcinoma (FL-HCC) tumor tissue; the fusion protein retains kinase activity in a cell culture assay. Immunoprecipitation, Western blot, cell culture kinase assay, RNA sequencing Science High 24578576
2017 Expression of the DNAJB1-PRKACA fusion protein (via CRISPR-Cas9 or transposon-mediated gene transfer) is sufficient to drive liver tumor formation in mice resembling human FL-HCC; overexpression of wild-type PRKACA alone does not fully recapitulate the oncogenic activity, indicating the DNAJB1 portion contributes to oncogenesis beyond mere PRKACA overexpression. The fusion kinase interacts with β-catenin, and tumorigenesis is enhanced by genetic Wnt pathway activation. CRISPR-Cas9 genome editing, transposon-mediated somatic gene transfer, mouse tumor models, Co-IP for β-catenin interaction Proceedings of the National Academy of Sciences of the United States of America High 28923495 29162699
1997 Human Hsp40 (DNAJB1) acts as a co-chaperone for Hsp70 in mammalian cells: Hsp40 alone does not protect luciferase from heat inactivation and slightly increases heat sensitivity, but when co-expressed with human Hsp70, it accelerates luciferase reactivation from the heat-inactivated state. This Hsp40/Hsp70 chaperone activity operates in both cytoplasm and nucleus. Co-transfection in hamster fibroblasts, luciferase heat-inactivation and reactivation assays, subcellular-targeted luciferase constructs The Journal of biological chemistry High 9407119
2020 DNAJB1 (Hdj1) phase-separates into ubiquitin-rich nuclear bodies under basal conditions and into stress granules upon stress; this phase separation is driven by its G/F-rich region. Mutations in the G/F region impair Hdj1 phase separation and its incorporation into stress granules, and abrogate co-phase separation with FUS. Co-phase separation of Hdj1 with FUS stabilizes the liquid phase of FUS against amyloid aggregation in vitro and reduces abnormal FUS aggregation in cells. Different domains of Hdj1 mediate FUS phase separation versus suppression of FUS amyloid aggregation. Live-cell fluorescence imaging, in vitro phase separation assay, G/F-region mutagenesis, domain-swap experiments, FUS aggregation assays Proceedings of the National Academy of Sciences of the United States of America High 33229560
2022 DNAJB1 contains a specific HTT-binding motif (HBM) in the hinge region between CTD-I and CTD-II that binds the proline-rich domain (PRD) of soluble and aggregated Huntingtin (HTTExon1). Mutation H244A in the HBM completely abolishes DNAJB1-mediated suppression and disaggregation of HTT fibrils by the trimeric Hsc70/DNAJB1/Apg2 chaperone complex without affecting processing of other substrates. Overexpression of wild-type DNAJB1 but not DNAJB1-H244A prevents HTTExon1Q97 aggregate accumulation in HEK293 cells. In vitro disaggregation/suppression assays, site-directed mutagenesis (H244A), HEK293 cell aggregation assay, binding studies Nature communications High 35948542
2017 DNAJB1 (HSP40) suppresses MDA5 multimer formation upon dsRNA stimulation, thereby dampening MDA5/MAVS-mediated type I interferon induction. DNAJB1 interacts with MDA5 (identified by yeast two-hybrid), and upon dsRNA stimulation, DNAJB1 and HSP70 are co-upregulated and translocate to stress granules where MDA5 encounters dsRNA. Knockdown of endogenous DNAJB1 increases MDA5-MAVS-mediated IFN promoter activation and renders cells more virus-resistant. Yeast two-hybrid, Co-IP, IFN promoter reporter assay, knockdown (siRNA), immunofluorescence/co-localization Journal of innate immunity Medium 29069650
2016 DNAJB1 (Hsp40/DnaJB1) facilitates nuclear import of influenza A virus ribonucleoproteins (vRNPs): it interacts with NP via the J-domain of Hsp40 and the N-terminal region of NP, promotes NP association with importin-α, and is required for efficient vRNP nuclear import and viral polymerase function. RNAi or pharmacological inhibition of Hsp40 reduces vRNP nuclear import and attenuates viral replication. Co-IP, domain-mapping (J-domain mutants, NP N-terminal deletion), RNAi knockdown, nuclear import assay, viral replication assay Scientific reports Medium 26750153
2011 Influenza A virus nucleoprotein (NP) interacts with Hsp40 (DNAJB1) identified by yeast two-hybrid and confirmed by Co-IP in mammalian cells; NP expression coincides with dissociation of P58(IPK) from Hsp40 and decreased PKR phosphorylation, revealing NP as the viral factor that activates P58(IPK)-mediated PKR inhibition through its interaction with the Hsp40/P58(IPK) complex. Yeast two-hybrid, Co-IP in mammalian cells, immunofluorescence co-localization, siRNA knockdown, PKR phosphorylation assay PloS one Medium 21698289
2010 Influenza A and B virus M2 proteins interact with Hsp40 (DNAJB1) mapped to the CTD1 domain of Hsp40 (in vitro and in vivo); M2-Hsp40 interaction facilitates formation of a stable M2-Hsp40-P58(IPK) complex, enhancing PKR autophosphorylation and inducing cell death. Yeast two-hybrid, in vitro binding, Co-IP in mammalian cells, domain-mapping, PKR phosphorylation assay Protein & cell Medium 21204021
2014 DNAJB1 interacts with PDCD5 (identified by yeast two-hybrid) and induces ubiquitin-dependent proteasomal degradation of PDCD5, thereby suppressing p53-mediated apoptosis. The DNAJB1 domain required for PDCD5 interaction maps to residues 180-210 (D5 domain). DNAJB1 knockdown in A549 cells increases PDCD5 levels, activates p53-dependent apoptosis genes, and reduces cancer cell growth in a p53-dependent manner. Yeast two-hybrid, Co-IP, domain-mapping, ubiquitination assay, siRNA knockdown, luciferase/reporter assays Cancer letters Medium 25444898
2015 DNAJB1 interacts with MIG6 (identified by yeast two-hybrid) and destabilizes MIG6 protein through K48-linked ubiquitination, promoting EGFR signaling. DNAJB1 knockdown increases MIG6 protein levels and reduces EGFR pathway activation. This DNAJB1-mediated MIG6 destabilization modulates sensitivity to the EGFR inhibitor gefitinib. Yeast two-hybrid, Co-IP, ubiquitination assay, siRNA knockdown, EGFR signaling readouts Biochimica et biophysica acta Medium 26239118
2013 DNAJB1 specifically binds MDM2 (but not MDMX) via its C-terminus, identified by yeast two-hybrid and confirmed by in vitro and in vivo binding assays. DNAJB1 stabilizes MDM2 at the post-translational level by inhibiting MDM2 ubiquitin-mediated degradation. In cancer cells, DNAJB1 depletion accelerates MDM2 degradation and reduces p53 pathway activity in a p53-dependent manner, enhancing Rb/E2F pathway activity and promoting cell growth. Yeast two-hybrid, Co-IP, in vitro binding, siRNA knockdown, ubiquitination assay, in vitro and in vivo cell growth assays Biochimica et biophysica acta Medium 24361594
2002 Hsp40 (DNAJB1) and Hsp70 together co-localize with intracytoplasmic aggregates of mutant SOD1 in cultured neuronal cells; their combined overexpression (but not either alone) reduces aggregate formation and markedly improves neurite outgrowth, and prevents cell death to a lesser extent. Co-transfection in neuronal cell culture, immunofluorescence co-localization, aggregate quantification, neurite outgrowth assay Brain research Medium 12213295
2001 In an in vitro reconstituted system with purified proteins, Hsp40 binding to the progesterone receptor (PR) is the first step in the HSP90 chaperoning pathway, preceding HSP70 binding; this occurs rapidly, independently of ATP or other proteins, with ~1:1 stoichiometry and Kd = 77 nM. The Hsp40·PR complex can then progress to hormone-binding competent PR upon addition of the other chaperones. Purified protein reconstitution, antibody pull-down, equilibrium binding analysis, hormone-binding activity assay The Journal of biological chemistry High 11809754
2019 Hsp40 (including DNAJB1-class members) and Hsp70 inhibit androgen receptor (AR) transcriptional activity by recognizing a region of the AR N-terminal domain (NTD) including the FQNLF motif, competing with the AR ligand-binding domain for this motif and thereby maintaining AR in an inactive conformation. Hsp70 binding increases NTD solubility; stabilizing NTD-Hsp70 interaction with small molecules reduces AR aggregation and promotes its degradation in cell and mouse models of SBMA. Co-IP, pulldown with purified proteins, small-molecule stabilization assays, cellular and mouse model functional readouts Nature communications Medium 31395886
2018 DNAJB1 (Hsp40) is present in a multiprotein complex with full-length AR, ARv7, and Hsp70 in CRPC cells (pulldown with biotinylated compound C86 and binding with purified proteins). Inhibition of Hsp40 by C86 or allosteric Hsp70 inhibition destabilizes both full-length AR and AR splice variants (including ARv7 lacking the ligand-binding domain), reducing their transcriptional activity. Biotinylated-compound pulldown, binding studies with purified proteins, cell-based protein stability and transcription assays, xenograft tumor model Cancer research Medium 29764864
2022 Sirt1 interacts with Dnajb1 and promotes its deacetylation and reduces its ubiquitination; Sirt1 overexpression upregulates Dnajb1 expression and enhances chaperone-mediated autophagy (CMA) activity after closed head injury. Knockdown of Dnajb1 abolishes the Sirt1-mediated attenuation of astrocyte activation and CMA upregulation. Co-IP, lentiviral overexpression and shRNA knockdown, in vivo CHI model, CMA activity assay, deacetylation/ubiquitination assays Cerebral cortex Medium 35106540
1996 The human DNAJB1 gene (then HSPF1) is located on chromosome 19p13.2, is composed of three exons divided by two introns, has a GC-rich 5' region, and its promoter contains heat shock elements (HSEs) bound by HSF1, confirming it is a bona fide heat shock protein gene. Genomic cloning, in situ hybridization, promoter deletion analysis Genomics Medium 8975727
1998 The human DNAJB1 (Hsp40) promoter contains eight contiguous HSE (AGAAN) motifs essential for heat shock response; the major transcription initiation site is 47 bp upstream of the ATG codon. In vivo footprinting confirms HSF1 binds these elements to drive heat-inducible transcription. 5' and 3' RACE, primer extension, deletion constructs/reporter assays, gel mobility supershift with HSF1 antibody, in vivo footprinting Biochimica et biophysica acta Medium 9545528
2016 DNAJB1 is a transcriptional target of the lens transcription factor FOXE3: chromatin immunoprecipitation and luciferase assays confirm FOXE3 directly regulates DNAJB1 expression. Knockdown of DNAJB1 in human lens epithelial cells causes mitotic arrest, and morpholino-mediated knockdown of dnajb1a in zebrafish produces underdeveloped cataractous lenses with persistent apoptotic nuclei. Chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown (cell cycle analysis), zebrafish morpholino knockdown Nature communications Medium 27218149
2018 Cytosolic Hsp70 and its Hsp40 co-chaperones (including the mammalian DNAJB1-class Sis1 ortholog) interact with newly synthesized mitochondrial β-barrel proteins; inhibiting Hsp70 activity or depleting Hsp40 co-chaperones reduces import of β-barrel proteins into mitochondria in both yeast and mammalian cells. Co-IP with newly synthesized proteins, Hsp70 activity inhibition, Hsp40 depletion, import assays in yeast and mammalian cells The Journal of cell biology Medium 29930205
2019 DNAJB1 knockout (CRISPR-Cas9) in HEK293 cells does not affect seeded α-synuclein aggregation induced by pre-formed fibrils, demonstrating that DNAJB1 is not required for suppression of this specific aggregation pathway (negative result; DNAJB6 KO, in contrast, significantly increases aggregation). CRISPR-Cas9 KO, α-Syn PFF seeding, fluorescence microscopy, FRET analysis International journal of molecular sciences Medium 31514384
2017 Overexpression of the mammalian Sis1 homologue DNAJB1 reduces toxicity arising from overexpressed TDP-43 and FUS in primary rodent cortical neurons and human embryonic kidney cells, as measured by cell viability; no direct physical association between Sis1/DNAJB1 and TDP-43 was detected, suggesting an indirect effect on aggregation. Neuronal cell overexpression, cell viability assay, co-IP (negative result for direct Sis1-TDP43 binding) PLoS genetics Medium 28531192
2008 TAT-fused Hsp40 (DNAJB1) transduced into cells reduces ubiquitin-proteasome-mediated degradation of Hsp70 under oxidative stress conditions (H2O2 treatment), thereby protecting cells from cytotoxicity; Hsp40 prevents ubiquitination of Hsp70. TAT-fusion protein transduction, cell viability assay, ubiquitination analysis, Hsp70 degradation assay FEBS letters Low 18258197
2023 Continued expression of DNAJB1-PRKACA is required not only for tumor maintenance but for tumor cell survival; inducible shRNA knockdown targeting the fusion junction kills FL-HCC patient-derived xenograft (PDX) cells in vitro and inhibits tumor growth in vivo, demonstrating oncogenic addiction to the fusion kinase. Inducible shRNA (tiling fusion junction), PDX cell viability, in vivo xenograft inhibition Clinical cancer research Medium 36302174
2014 HSP40 (DNAJB1) interacts with pyruvate kinase M2 (PKM2) and, together with HSC70, destabilizes PKM2 protein, reducing PKM2-dependent PDK1 expression and glycolysis while affecting mitochondrial oxygen respiration and cancer cell proliferation. Co-IP (HSP40-PKM2), protein stability assay, siRNA knockdown, metabolic assays (glycolysis, respiration), cell proliferation assay PloS one Low 24658033

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cellular and molecular life sciences : CMLS 689 16952052
2014 Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science (New York, N.Y.) 390 24578576
2004 Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nature structural & molecular biology 240 15543156
2005 Not all J domains are created equal: implications for the specificity of Hsp40-Hsp70 interactions. Protein science : a publication of the Protein Society 231 15987899
1998 Protein folding activity of Hsp70 is modified differentially by the hsp40 co-chaperones Sis1 and Ydj1. The Journal of biological chemistry 188 9774392
1991 Characterization of SIS1, a Saccharomyces cerevisiae homologue of bacterial dnaJ proteins. The Journal of cell biology 178 1714460
2008 Specificity of the J-protein Sis1 in the propagation of 3 yeast prions. Proceedings of the National Academy of Sciences of the United States of America 148 18955697
1997 Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells. The Journal of biological chemistry 147 9407119
2008 Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. The EMBO journal 144 18833196
2001 Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53. The EMBO journal 142 11707401
2000 The crystal structure of the peptide-binding fragment from the yeast Hsp40 protein Sis1. Structure (London, England : 1993) 142 10997899
2000 Molecular chaperone function of mammalian Hsp70 and Hsp40--a review. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 140 10830586
2017 DNAJB1-PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America 139 29162699
1993 The yeast SIS1 protein, a DnaJ homolog, is required for the initiation of translation. Cell 129 8513501
2015 DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 128 25698061
2010 Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40. ACS chemical biology 128 20481474
2019 Structural basis for client recognition and activity of Hsp40 chaperones. Science (New York, N.Y.) 124 31604242
2015 Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae. RNA (New York, N.Y.) 120 26199455
2000 Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell stress & chaperones 113 11147971
2007 The Hsp40 proteins of Plasmodium falciparum and other apicomplexa: regulating chaperone power in the parasite and the host. The international journal of biochemistry & cell biology 110 17428722
2002 HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. The Journal of biological chemistry 109 11809754
2018 Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer. Cancer research 106 29764864
2019 DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 104 31676785
2019 Structural and functional analysis of the Hsp70/Hsp40 chaperone system. Protein science : a publication of the Protein Society 103 31509306
2003 Specificity of class II Hsp40 Sis1 in maintenance of yeast prion [RNQ+]. Molecular biology of the cell 102 12631732
2016 Dynamical Structures of Hsp70 and Hsp70-Hsp40 Complexes. Structure (London, England : 1993) 97 27345933
2020 Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles. Proceedings of the National Academy of Sciences of the United States of America 95 33229560
2017 CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma. Gastroenterology 87 28923495
2002 Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1. Brain research 83 12213295
2018 Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins. The Journal of cell biology 80 29930205
2007 J-protein co-chaperone Sis1 required for generation of [RNQ+] seeds necessary for prion propagation. The EMBO journal 79 17673909
2002 Identification of essential residues in the type II Hsp40 Sis1 that function in polypeptide binding. The Journal of biological chemistry 69 11919183
2002 Increased expression of Hsp40 chaperones, transcriptional factors, and ribosomal protein Rpp0 can cure yeast prions. The Journal of biological chemistry 69 11923285
2013 The Type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein. PloS one 66 23341891
2011 Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation. PloS one 62 21698289
2001 The yeast hsp70 homologue Ssa is required for translation and interacts with Sis1 and Pab1 on translating ribosomes. The Journal of biological chemistry 61 11279042
2019 Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor. Nature communications 60 31395886
2016 Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins. Scientific reports 58 26750153
2022 The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma. Nature communications 56 36302754
2006 Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperone pathway. The Journal of biological chemistry 56 16854979
2010 Hsp90 and Hsp40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1. Oncogene 55 20418907
2018 Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1-PRKACA fusion. Hepatology (Baltimore, Md.) 53 29222914
2006 Crystal structure of yeast Sis1 peptide-binding fragment and Hsp70 Ssa1 C-terminal complex. The Biochemical journal 53 16737444
2005 In vivo bipartite interaction between the Hsp40 Sis1 and Hsp70 in Saccharomyces cerevisiae. Genetics 49 15687271
2015 Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone Sis1. Journal of molecular biology 47 25687964
2014 Myopathy-causing mutations in an HSP40 chaperone disrupt processing of specific client conformers. The Journal of biological chemistry 47 24920671
2017 Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis. PLoS genetics 45 28531192
2004 Expression of HSPF1 and LIM in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia. Journal of human genetics 45 15362566
2015 Specification of Hsp70 function by Type I and Type II Hsp40. Sub-cellular biochemistry 44 25487017
2002 Direct interactions between molecular chaperones heat-shock protein (Hsp) 70 and Hsp40: yeast Hsp70 Ssa1 binds the extreme C-terminal region of yeast Hsp40 Sis1. The Biochemical journal 44 11743879
2022 NudC guides client transfer between the Hsp40/70 and Hsp90 chaperone systems. Molecular cell 43 35063133
2017 The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer. The EMBO journal 43 28655754
2018 DnaJ/Hsp40 Family and Parkinson's Disease. Frontiers in neuroscience 42 29367843
2014 DNAJB1 destabilizes PDCD5 to suppress p53-mediated apoptosis. Cancer letters 42 25444898
2018 Hsp40/70/110 chaperones adapt nuclear protein quality control to serve cytosolic clients. The Journal of cell biology 40 29653997
2015 Mitochondrial heat shock protein machinery hsp70/hsp40 is indispensable for proper mitochondrial DNA maintenance and replication. mBio 40 25670781
2011 Heat shock protein 40 (Hsp40) plays a key role in the virus life cycle. Virus research 40 21729725
2021 Subcellular localization of the J-protein Sis1 regulates the heat shock response. The Journal of cell biology 39 33326013
2016 FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1. Nature communications 39 27218149
2019 The Molecular Chaperone DNAJB6, but Not DNAJB1, Suppresses the Seeded Aggregation of Alpha-Synuclein in Cells. International journal of molecular sciences 38 31514384
2021 Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins. Proceedings of the National Academy of Sciences of the United States of America 37 34873058
2012 Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism. PloS one 37 23226463
2009 Inhibition of Hsp27 and Hsp40 potentiates 5-fluorouracil and carboplatin mediated cell killing in hepatoma cells. Cancer biology & therapy 37 19901540
2014 HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells. PloS one 36 24658033
2014 Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection. PLoS genetics 36 25058638
2010 Interaction of Hsp40 with influenza virus M2 protein: implications for PKR signaling pathway. Protein & cell 36 21204021
2018 HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling. Theranostics 35 30083263
2015 DNAJB1 negatively regulates MIG6 to promote epidermal growth factor receptor signaling. Biochimica et biophysica acta 35 26239118
2006 JDP1 (DNAJC12/Hsp40) expression in breast cancer and its association with estrogen receptor status. International journal of molecular medicine 35 16391838
1997 Modulation of intracellular protein degradation by SSB1-SIS1 chaperon system in yeast S. cerevisiae. FEBS letters 35 9202167
2020 Sis1 potentiates the stress response to protein aggregation and elevated temperature. Nature communications 34 33293525
2016 Protein arginylation regulates cellular stress response by stabilizing HSP70 and HSP40 transcripts. Cell death discovery 33 27752365
2014 Genome-wide identification of hsp40 genes in channel catfish and their regulated expression after bacterial infection. PloS one 33 25542027
2012 Identification of regions involved in substrate binding and dimer stabilization within the central domains of yeast Hsp40 Sis1. PloS one 32 23227221
2018 Overexpression of a conserved HSP40 chaperone reduces toxicity of several neurodegenerative disease proteins. Prion 30 29308690
2012 A Hsp40 chaperone protein interacts with and modulates the cellular distribution of the primase protein of human cytomegalovirus. PLoS pathogens 30 23133382
2017 DNAJB1/HSP40 Suppresses Melanoma Differentiation-Associated Gene 5-Mitochondrial Antiviral Signaling Protein Function in Conjunction with HSP70. Journal of innate immunity 29 29069650
2016 The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x. PloS one 29 26845441
2021 Role of the DNAJ/HSP40 family in the pathogenesis of insulin resistance and type 2 diabetes. Ageing research reviews 27 33676026
2014 Plasmodial Hsp40 and Hsp70 chaperones: current and future perspectives. Parasitology 27 24666996
2009 Prion propagation by Hsp40 molecular chaperones. Prion 27 19535913
2004 Hsp70 and Hsp40 chaperones do not modulate retinal phenotype in SCA7 mice. The Journal of biological chemistry 27 15494410
2023 Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA. Clinical cancer research : an official journal of the American Association for Cancer Research 26 36302174
2022 Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT. Nature communications 26 35948542
2023 Mechanisms of Protein Quality Control in the Endoplasmic Reticulum by a Coordinated Hsp40-Hsp70-Hsp90 System. Annual review of biophysics 25 37159299
2008 TAT-Hsp40 inhibits oxidative stress-mediated cytotoxicity via the inhibition of Hsp70 ubiquitination. FEBS letters 25 18258197
2002 Characterization and functional analysis of a heart-enriched DnaJ/ Hsp40 homolog dj4/DjA4. Cell stress & chaperones 25 12380683
1998 Characterization of HSE sequences in human Hsp40 gene: structural and promoter analysis. Biochimica et biophysica acta 25 9545528
2022 Sirt1 attenuates astrocyte activation via modulating Dnajb1 and chaperone-mediated autophagy after closed head injury. Cerebral cortex (New York, N.Y. : 1991) 24 35106540
2022 Active unfolding of the glucocorticoid receptor by the Hsp70/Hsp40 chaperone system in single-molecule mechanical experiments. Proceedings of the National Academy of Sciences of the United States of America 24 35377810
2022 The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity. EMBO molecular medicine 23 35373908
2021 Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites. mBio 23 34182772
2018 Variant-specific and reciprocal Hsp40 functions in Hsp104-mediated prion elimination. Molecular microbiology 23 29633387
2011 Central domain deletions affect the SAXS solution structure and function of yeast Hsp40 proteins Sis1 and Ydj1. BMC structural biology 23 22011374
2023 Specification of Hsp70 Function by Hsp40 Co-chaperones. Sub-cellular biochemistry 22 36520305
2022 Plasma membrane-localized Hsp40/DNAJ chaperone protein facilitates OsSUVH7-OsBAG4-OsMYB106 transcriptional complex formation for OsHKT1;5 activation. Journal of integrative plant biology 22 36349953
2019 Hsp40 Protein DNAJB6 Interacts with Viral NS3 and Inhibits the Replication of the Japanese Encephalitis Virus. International journal of molecular sciences 22 31739611
1996 Genomic cloning of a human heat shock protein 40 (Hsp40) gene (HSPF1) and its chromosomal localization to 19p13.2. Genomics 22 8975727
2018 Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition. PloS one 21 30118500
2013 DNAJB1 stabilizes MDM2 and contributes to cancer cell proliferation in a p53-dependent manner. Biochimica et biophysica acta 21 24361594

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