Affinage

Showing DNAJC2 — ZRF1 is a alias.

DNAJC2

DnaJ homolog subfamily C member 2 · UniProt Q99543

Length
621 aa
Mass
72.0 kDa
Annotated
2026-06-09
48 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAJC2 (ZRF1/MPP11/Zuo1) is a dual-function J-domain protein that bridges co-translational protein folding at the ribosome and chromatin-based epigenetic regulation in the nucleus (PMID:16002468, PMID:21179169). In its cytosolic role, it is the J-protein subunit of the ribosome-associated complex (RAC), forming a stable complex with the Hsp70-related Ssz1/Hsp70L1 that targets the ribosome and stimulates the ATPase of a partner Hsp70 (Ssb in yeast, Hsc70 in mammals) to fold nascent chains (PMID:11274393, PMID:16002468, PMID:15908962); the mammalian protein functionally substitutes for yeast Zuo1, establishing deep conservation of this activity (PMID:15802566). It engages the ribosome through a bipartite contact, with its N-terminus near the 60S exit tunnel (eL31, 25S rRNA helix 24) and its C-terminus on the 40S subunit (18S rRNA ES12), and these contacts control translational fidelity including stop-codon readthrough and frameshifting (PMID:27669034). Through the RAC/Ssb system DNAJC2 also couples translation to nutrient and organellar signaling, being required to lower protein synthesis upon TORC1 inhibition (PMID:37984430). In the nucleus, DNAJC2 is recruited to chromatin via a ubiquitin-interacting domain within its conserved zuotin homology domain that binds monoubiquitinated histone H2A-K119, displacing Polycomb-repressive complex 1 (PRC1) to activate Polycomb target genes during differentiation (PMID:21179169, PMID:21311219); this activity drives neural progenitor specification through Pax6 and Wnt genes (PMID:24449271) and is gated by direct interaction with Id1, which blocks its chromatin recruitment (PMID:25361733). The same chromatin function operates in oncogene-induced senescence at the INK4-ARF locus and is phosphorylated on Ser47 by S6 kinases downstream of mTORC1 (PMID:22733129, PMID:28242756), and in leukemia it cooperates with retinoic acid receptor alpha to control transcription of RA target genes (PMID:24292673). DNAJC2 additionally functions in genome maintenance, remodeling E3 ubiquitin ligase complexes and recruiting DICER at UV-damaged chromatin to promote global genome nucleotide excision repair (PMID:27091446, PMID:28402505), and it binds and stabilizes G-quadruplex DNA structures to recruit NER factors and preserve genome stability (PMID:32764578, PMID:41182900). Genetically, DNAJC2 is essential for early mouse post-implantation development (PMID:31230751).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 Medium

    The founding question was whether the yeast ZUO1 product had a nucleic-acid-related activity; identifying it as a Z-DNA binding protein with a growth phenotype gave the gene its first biochemical and physiological footing.

    Evidence Z-DNA binding/Southwestern assays with recombinant protein and ZUO1 disruption in yeast

    PMID:1396572

    Open questions at the time
    • Z-DNA binding never connected mechanistically to later ribosome or chromatin roles
    • single lab, no structural basis for binding
  2. 1998 High

    Whether Zuo1 acted in translation was resolved by showing it is a ribosome-associated DnaJ protein whose deletion phenocopies Ssb Hsp70 loss, placing it as a co-chaperone on the ribosome.

    Evidence Ribosome fractionation, deletion/truncation mutants, and phenotypic epistasis in yeast

    PMID:9707440

    Open questions at the time
    • Did not define the partner Hsp70 mechanism or substrate spectrum
    • ribosome contact sites unknown
  3. 2001 High

    The molecular assembly was defined by showing Zuo1 and Ssz1 form a stable 1:1 ribosome-associated complex (RAC) with chaperone-like activity on nascent chains, converting the co-chaperone hypothesis into a defined complex.

    Evidence Co-purification, genetic deletion, and in vitro nascent-chain translocation assays

    PMID:11274393

    Open questions at the time
    • Catalytic mechanism of Zuo1's J-domain toward Hsp70 not yet shown
    • human conservation untested at this point
  4. 2005 High

    RAC's conservation and enzymatic logic were established: human MPP11/Hsp70L1 reconstitutes RAC and complements yeast, and Ssz1 potentiates Zuo1's J-protein stimulation of Ssb ATPase independent of its own ATP hydrolysis.

    Evidence Reciprocal co-purification, yeast complementation, in vitro ATPase assays with extensive ATP-cleft mutagenesis

    PMID:15802566 PMID:15908962 PMID:16002468

    Open questions at the time
    • Mammalian nascent-chain substrates not catalogued
    • structural basis of Hsp70 stimulation unresolved
  5. 2004 Medium

    A ribosome-independent moonlighting function emerged: the Zuo1 C-terminal domain (and Ssz1 ATPase domain) activates transcription factor Pdr1 to induce drug resistance only after dissociation from the ribosome.

    Evidence Domain deletion, overexpression, and genetic epistasis in yeast

    PMID:15225326

    Open questions at the time
    • Trigger for ribosome release not defined here
    • direct Zuo1-Pdr1 contact not yet shown
  6. 2010 High

    The nuclear/epigenetic identity of the mammalian protein was discovered: ZRF1 binds monoubiquitinated H2A-K119 through a ubiquitin-interacting domain in its zuotin homology domain and displaces PRC1 to activate Polycomb targets, defining a chromatin function distinct from translation.

    Evidence Co-IP, ChIP/ChIP-seq, domain mutagenesis, and differentiation assays

    PMID:21179169

    Open questions at the time
    • How a ribosomal J-protein partitions to chromatin not explained
    • mechanism of subsequent gene activation only partly defined
  7. 2011 Medium

    The chromatin activation mechanism was refined into a two-step model in which ZRF1 displaces PRC1 and acts with H2A deubiquitinases; in parallel yeast work showed Zuo1/Ssz1 directly bind Pdr1 to drive a quorum-sensing growth-arrest program.

    Evidence ChIP, co-IP, reporter assays in mammalian cells; yeast two-hybrid, conditioned-medium and epistasis assays in yeast

    PMID:21311219 PMID:22203981

    Open questions at the time
    • Identity of the relevant deubiquitinases not pinned down
    • regulation of ZRF1 chromatin recruitment unaddressed
  8. 2012 High

    Structure and physiology of the two arms advanced: the Zuo1 C-terminal autoinhibitory 4-helix bundle must unfold (coupled to ribosome release) to activate Pdr1, and ZRF1 was shown to bind the INK4-ARF locus to enforce oncogene-induced senescence.

    Evidence NMR structure, yeast two-hybrid and PDR reporter assays; ChIP, siRNA, and oncogenic Ras proliferation assays

    PMID:22733129 PMID:23036859

    Open questions at the time
    • Upstream signal triggering 4HB unfolding unknown
    • how ZRF1 selects senescence-locus targets unresolved
  9. 2013 High

    A disease-relevant chromatin partnership was defined by showing ZRF1 interacts with RARalpha to control RA target gene transcription and leukemogenic potential in AML.

    Evidence Reciprocal co-IP, ChIP-seq, RNA-seq, siRNA, and xenograft model

    PMID:24292673

    Open questions at the time
    • Whether RARalpha interaction is direct or complex-mediated not fully separated
    • link to the H2A-ubiquitin/PRC1 mechanism not integrated
  10. 2014 Medium

    Developmental control and its gating were established: Zrf1 drives neural progenitor specification by displacing PRC1 at Pax6/Wnt genes, and Id1 directly binds Zrf1 to block its chromatin recruitment until differentiation.

    Evidence shRNA/siRNA knockdown, ChIP, ESC differentiation, in vivo cortical depletion; co-IP and rescue in ESCs

    PMID:24449271 PMID:25361733

    Open questions at the time
    • Signals controlling Id1 downregulation not defined
    • single-lab findings without orthogonal genetic confirmation
  11. 2016 High

    The physical basis of ribosome engagement and its functional consequence were resolved: Zuo1 spans both subunits (60S exit site and 40S ES12) and these contacts control translational fidelity; concurrently ZRF1 was shown to remodel UV-DDB/CUL4 E3 ligase complexes for nucleotide excision repair.

    Evidence Cryo-EM positioning, in vivo cross-linking, fidelity assays; co-IP, ChIP, siRNA, and GG-NER assays after UV

    PMID:27091446 PMID:27669034

    Open questions at the time
    • How translational-fidelity role relates to chaperone folding not fully separated
    • structural detail of ZRF1 in the E3 remodeling step lacking
  12. 2017 High

    Regulation and effectors of the repair/senescence arm advanced: S6 kinases phosphorylate ZRF1 on Ser47 downstream of mTORC1 to drive a senescence program, and ZRF1 recruits DICER to decondense UV-damaged chromatin via PARP1.

    Evidence Chemical-genetic S6K screen, in vivo phosphorylation and Ser47 mutagenesis, senescence assays; co-IP, chromatin fractionation, catalytic-mutant DICER assays

    PMID:28242756 PMID:28402505

    Open questions at the time
    • How Ser47 phosphorylation alters ZRF1 activity mechanistically unclear
    • DICER recruitment step single lab
  13. 2019 Medium

    Human structural features and organismal requirement were established: the human 4HB retains the 40S-binding charged helix but adds a linker to SANT domains absent in fungi, and Dnajc2 is essential for early mouse post-implantation development.

    Evidence NMR structure with evolutionary analysis; CRISPR knockout and 1-cell embryo siRNA knockdown in mice

    PMID:31091298 PMID:31230751

    Open questions at the time
    • Function of human-specific SANT linker not validated
    • which DNAJC2 activity drives the embryonic lethality unresolved
  14. 2020 High

    A direct genome-stability function was defined by showing Zuo1 binds G4-DNA in vitro and in vivo and recruits NER factors, linking the protein's original DNA-binding capacity to repair and genome integrity.

    Evidence In vitro and in vivo G4 binding, NER recruitment, UV-sensitivity, and genetic analysis in yeast

    PMID:32764578

    Open questions at the time
    • G4-binding domain not yet mapped at residue level here
    • relationship between G4 and ribosome roles unclear
  15. 2023 Medium

    The translation-stress and human G4 functions were extended: RAC/Ssb is required to reduce translation and degrade eIF4G under TORC1 inhibition, NAC and Zuotin/Hsp70 can co-occupy the exit tunnel, and human ZRF1 is recruited to UV-induced G4 structures to ensure proper lesion repair and prevent senescence.

    Evidence Yeast zuo1delta translation/autophagy assays under rapamycin; in vivo cross-linking + MS; G4 immunofluorescence, ZRF1 ChIP-seq, and senescence assays after UV

    PMID:37872164 PMID:37984430 PMID:38224454

    Open questions at the time
    • Direct ZRF1-G4 binding domain in human not defined here
    • coordination of NAC and RAC at the tunnel functionally unresolved
  16. 2025 Low

    The structural and signaling boundaries of the G4 and stress roles were refined: the Zuo1 C-terminus (348-433) binds and stabilizes specific G4 conformations, and Zuo1 acts in a pathway that mutes translation upon mitochondrial dysfunction.

    Evidence NMR and smFRET with in vivo G4 detection; yeast genetic epistasis with translation readouts (preprint for the mitochondrial-stress work)

    PMID:41182900 PMID:bio_10.1101_2025.08.21.671487

    Open questions at the time
    • Mitochondrial-stress finding is a preprint, single lab, awaiting peer review
    • how G4 binding by the C-terminus integrates with ribosome-binding C-terminal contacts unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single protein physically and temporally partitions between ribosome-associated chaperone duty and nuclear chromatin/genome-maintenance roles, and whether these functions share a regulatory switch, remains unresolved.
  • No defined trafficking or signal partitioning ZRF1 between ribosome and chromatin
  • no human disease-causing mutation reported in the corpus
  • substrate spectrum of the mammalian RAC chaperone uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0003723 RNA binding 2 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005840 ribosome 4 GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1266738 Developmental Biology 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
BRD4DICER1ID1PDR1RARARING1BSSB/HSC70SSZ1/HSP70L1
Complex memberships
RAC (ribosome-associated complex; Zuo1/DNAJC2-Ssz1/Hsp70L1)UV-DDB-CUL4A E3 ligase complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Zuotin (ZUO1/DNAJC2 yeast ortholog) was identified as a Z-DNA binding protein purified from yeast nuclear extract; the cloned and expressed protein showed Z-DNA binding activity, and disruption of ZUO1 resulted in a slow growth phenotype. Z-DNA binding assay, Southwestern blot, gene cloning and expression in E. coli, ZUO1 gene disruption The EMBO journal Medium 1396572
1998 Zuo1 (yeast DNAJC2 ortholog) is a ribosome-associated DnaJ-related protein localized predominantly in the cytosol; ribosome association correlates with RNA binding ability, and zuo1 deletion phenotypes (cold sensitivity, aminoglycoside sensitivity, osmosensitivity) resemble those of Ssb Hsp70 deletion, placing Zuo1 as a co-chaperone with Ssb on the ribosome. Deletion and truncation mutant analysis, ribosome fractionation, phenotypic characterization The EMBO journal High 9707440
2001 Zuo1 (yeast DNAJC2 ortholog) and the DnaK homolog Ssz1p form a stable 1:1 ribosome-associated complex (RAC) in yeast; Zuo1 mediates ribosome binding of the complex; RAC stimulates translocation of a ribosome-bound mitochondrial precursor protein into mitochondria in vitro, demonstrating chaperone-like activity on nascent chains. Co-purification, in vitro translocation assay, genetic deletion analysis Proceedings of the National Academy of Sciences of the United States of America High 11274393
2005 Human MPP11 (DNAJC2) localizes to the cytosol and associates with ribosomes; it forms a stable complex with Hsp70L1 (a distant Ssz1p homolog), constituting the mammalian ribosome-associated complex (RAC); this complex is functional in yeast complementation experiments. Subcellular fractionation, co-purification/affinity purification, yeast complementation Proceedings of the National Academy of Sciences of the United States of America High 16002468
2005 Human Mpp11 (DNAJC2) functionally substitutes for yeast Zuo1 when expressed in yeast, partnering with the multifunctional Hsp70 Ssa (homolog of mammalian Hsc70) rather than Ssb, demonstrating that ribosome-associated J-protein chaperone function is conserved in metazoans. Yeast complementation assay, genetic epistasis Science (New York, N.Y.) High 15802566
2005 Zuo1 (yeast DNAJC2 ortholog) is the J-protein partner of the ribosome-associated Hsp70 Ssb; Zuo1 efficiently stimulates Ssb ATPase activity only when in complex with Ssz1; Ssz1 ATP-binding and hydrolysis are not required for its function in vivo, indicating Ssz1's primary role is to potentiate Zuo1's J-protein activity toward Ssb. ATPase activity assay in vitro, site-directed mutagenesis of ATP-binding cleft (11 substitutions), in vivo functional analysis Nature structural & molecular biology High 15908962
2004 The C-terminal domain of Zuo1 (yeast DNAJC2 ortholog), dispensable for ribosome-associated chaperone function, is necessary and sufficient to activate the transcription factor Pdr1 and induce pleiotropic drug resistance (PDR); Ssz1's N-terminal ATPase domain is also sufficient for PDR induction independently; Ssb has no role in PDR; both Ssz1 and Zuo1 must be dissociated from ribosomes to induce PDR. Domain deletion analysis, overexpression studies, genetic epistasis Molecular microbiology Medium 15225326
2010 ZRF1 (human DNAJC2) is specifically recruited to chromatin via a novel ubiquitin-interacting domain located within its evolutionarily conserved zuotin domain, binding monoubiquitinated histone H2A at Lys119; upon differentiation, ZRF1 displaces Polycomb-repressive complex 1 (PRC1) from chromatin and facilitates transcriptional activation of Polycomb target genes genome-wide. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), genome-wide mapping (ChIP-seq), domain mutagenesis, cell differentiation assays Nature High 21179169
2011 ZRF1 (DNAJC2) binds monoubiquitinated histone H2A, displaces PRC1 from chromatin, and subsequently acts together with H2A-specific deubiquitinases to facilitate transcriptional activation of Polycomb target genes in a two-step mechanism. Chromatin immunoprecipitation, co-immunoprecipitation, functional reporter assays Cell cycle (Georgetown, Tex.) Medium 21311219
2012 Zuo1's C-terminal 69 residues fold into an autoinhibitory left-handed four-helix bundle (4HB) that sequesters hydrophobic residues required for direct interaction with Pdr1; unfolding of this 4HB is required for Pdr1 activation, and destabilizing mutations cause both 4HB unfolding and ribosome dissociation of Zuo1 prior to Pdr1 activation. NMR structure determination of C-terminal domain, yeast two-hybrid interaction assay, site-directed mutagenesis, in vivo PDR reporter assay Journal of molecular biology High 23036859
2012 ZRF1 (DNAJC2) binds to the promoters of p15INK4b, ARF, and p16INK4a at the INK4-ARF locus during oncogene-induced senescence; ZRF1 depletion in oncogenic Ras-expressing cells restores proliferation by preventing Arf and p16Ink4a expression and bypassing senescence. Chromatin immunoprecipitation, siRNA knockdown, oncogenic Ras expression, cell proliferation assays Oncogene Medium 22733129
2011 Zuo1 and Ssz1 (yeast DNAJC2 complex) activate the transcription factor Pdr1 through direct yeast two-hybrid interaction; this activation causes premature growth arrest during diauxic shift by inducing Pdr5 and Snq2 membrane transporters that export quorum-sensing molecules. Yeast two-hybrid, genetic epistasis, conditioned medium transfer experiment, overexpression studies Proceedings of the National Academy of Sciences of the United States of America Medium 22203981
2013 ZRF1 (DNAJC2) controls leukemogenic potential in AML by interacting with retinoic acid receptor alpha (RARα) and binding to RA target gene promoters; ZRF1 depletion decreases proliferation, induces apoptosis, and enhances differentiation; ZRF1 regulates transcription of ~half of RA target genes genome-wide. Co-immunoprecipitation (ZRF1-RARα interaction), ChIP-seq, RNA-seq, siRNA knockdown, xenograft mouse model Oncogene High 24292673
2014 Zrf1 (DNAJC2) is required for neural progenitor cell (NPC) specification from embryonic stem cells and for NPC self-renewal; it promotes expression of Pax6 and Wnt ligand genes by displacing PRC1 from their promoters; reactivation of Wnt signaling in Zrf1-depleted NPCs restores Pax6 expression and self-renewal. siRNA/shRNA knockdown, ChIP, in vitro ESC differentiation, in vivo cortical depletion Genes & development Medium 24449271
2014 Id1 protein directly interacts with Zrf1 (DNAJC2) in embryonic stem cells; this interaction blocks Zrf1 recruitment to chromatin, preventing activation of neural genes; upon differentiation, decreased Id1 expression permits Zrf1 chromatin binding and neural gene activation. Co-immunoprecipitation, ChIP, Id1 knockdown/knockout ESCs, rescue experiments EMBO reports Medium 25361733
2015 The zuotin homology domain (ZHD), shared between Zuo1 and Jjj1, is important for ribosome association of both proteins; an N-terminal Jjj1 fragment containing J-domain and ZHD is ribosome-associated and rescues zuo1Δ growth defects; Zuo1 and Jjj1 likely bind overlapping ribosome sites via their ZHDs. Ribosome fractionation, truncation mutant analysis, complementation assays, genetic phenotyping Biochimica et biophysica acta Medium 25639645
2016 Zuo1 (yeast DNAJC2 ortholog) spans both ribosomal subunits: its N-terminal region interacts near the 60S polypeptide-exit site with ribosomal protein eL31 and 25S rRNA helix 24, while its C-terminus interacts with 18S rRNA expansion segment 12 (ES12) of the 40S subunit; deletions in ES12 or the Zuo1 C-terminus alter stop codon readthrough and -1 frameshifting. Cryo-EM structural positioning, in vivo site-specific cross-linking, ribosomal deletion mutants, translational fidelity assays Nature structural & molecular biology High 27669034
2016 ZRF1 (DNAJC2) mediates remodeling of E3 ubiquitin ligase complexes at UV-damaged chromatin sites: it recognizes H2A-ubiquitin deposited by the UV-RING1B complex (DDB2-DDB1-CUL4B-RING1B) and promotes assembly of the UV-DDB-CUL4A complex (DDB1-DDB2-CUL4A-RBX1); ZRF1 is essential for global genome nucleotide excision repair (GG-NER) and its function is linked to damage recognition factor XPC. Co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, DNA repair assays, UV irradiation The Journal of cell biology High 27091446
2017 ZRF1 (DNAJC2) mediates recruitment of the endonuclease DICER to chromatin at UV-damaged sites; ZRF1 and DICER together decondense chromatin via PARP1 during nucleotide excision repair; DICER's chromatin decondensation role is independent of its catalytic activity. Co-immunoprecipitation, chromatin fractionation, UV irradiation, PARP1 assays, catalytic mutant DICER Nucleic acids research Medium 28402505
2017 ZRF1 (DNAJC2) is a substrate of S6 kinases downstream of mTORC1; S6 kinases phosphorylate ZRF1 on Ser47 in cultured cells and in mammalian tissues in vivo; knockdown of ZRF1 or expression of a phosphorylation-deficient Ser47 mutant blunts the S6 kinase-dependent senescence programme and alters p16 levels. Chemical genetic screen for S6K substrates, in vivo phosphorylation assays, site-directed mutagenesis (Ser47), siRNA knockdown, senescence assays The EMBO journal High 28242756
2019 The 4-helix bundle (4HB) domain of human DNAJC2/ZRF1 adopts a bundle-of-4-helices structure by NMR; the positive charge of Helix I (responsible for 40S interaction in yeast) is conserved in humans; the C-terminal helix IV in human is extended and serves as a linker to regulatory SANT domains absent in fungi. NMR structure determination, evolutionary sequence analysis, comparative structural analysis PloS one Medium 31091298
2019 DNAJC2/ZRF1 is required for early post-implantation mouse embryonic development; Dnajc2 knockout in mice leads to early lethality after implantation; siRNA knockdown of maternal Dnajc2 mRNA in 1-cell embryos impairs early preimplantation development. CRISPR/Cas9 knockout, siRNA knockdown in 1-cell embryos, embryo viability assessment Biochemical and biophysical research communications Medium 31230751
2020 Zuo1 (yeast DNAJC2 ortholog) is a novel G4-DNA binding protein in vitro and in vivo; in the absence of Zuo1, fewer G4 structures form, cell growth slows, and UV sensitivity increases; Zuo1 function at G4 structures recruits NER factors, promoting genome stability; cells lacking both functional NER and Zuo1 accumulate G4 structures accessible to translesion synthesis. G4-DNA binding assays in vitro, in vivo G4 detection, NER factor recruitment assays, UV sensitivity assays, genetic analysis Nature communications High 32764578
2006 Zuo1 (yeast DNAJC2 ortholog) interacts with inhibitory RNA (IRNA) and is required for cap-independent translation mediated by the 5' UTR of yeast TFIID mRNA; the DnaJ domain of Zuo1, which mediates Hsp70 interaction, significantly affects cap-independent translation. RNA-binding assay (IRNA-pulldown), ZUO1 deletion and domain mutant complementation, cap-independent translation reporter assay Biochemical and biophysical research communications Medium 17027912
2021 ZRF1 (DNAJC2) interacts with BRD4 and the circRNA-encoded protein p113 (from CUX1) to form a transcriptional regulatory complex; p113-ZRF1 interaction mediates transactivation of ZRF1/BRD4 target genes (ALDH3A1, NDUFA1, NDUFAF5) in neuroblastoma cells; a peptide blocking p113-ZRF1 interaction suppresses tumor aggressiveness. Co-immunoprecipitation, mass spectrometry, ChIP-seq, RNA-seq, inhibitory peptide experiments Molecular cancer Medium 34579723
2023 ZRF1 (DNAJC2) is recruited to UV-induced G4-DNA structures in cell nuclei upon UV irradiation; ZRF1 binding to G4s ensures genome stability and proper UV lesion repair; absence of ZRF1 causes G4 structure accumulation, improper UV lesion repair, upregulation of DDB2, and entry into senescence. G4 detection in cell nuclei (immunofluorescence/G4 antibody), ChIP-seq for ZRF1 at G4 sites, UV irradiation, senescence assays, DDB2 expression analysis Nature communications Medium 37872164
2023 The RAC/Ssb chaperone system (composed of Zuo1/DNAJC2 and Ssb Hsp70) is required to maintain proteostasis and cell viability under TORC1 inhibition; in the absence of Zuo1, translation does not decrease in response to TORC1 inhibition, and eIF4G degradation via autophagy is prevented, implicating Zuo1 in translational control downstream of TORC1 signaling. Genetic deletion (zuo1Δ), translation rate measurements, autophagy assays, eIF4G Western blot, TORC1 inhibitor (rapamycin) treatment The EMBO journal Medium 37984430
2024 NAC (nascent chain-associated complex) and Zuotin (DNAJC2 yeast ortholog)/Hsp70 can co-occupy the ribosome tunnel exit simultaneously in vivo; in vivo cross-linking shows Zuotin and NAC interact at the ribosome even during translation initiation inhibition; Hsp70 can position its peptide-binding site at the tunnel exit with Zuotin's J-domain appropriately positioned even in NAC's presence. In vivo site-specific cross-linking, ribosome fractionation, cross-link identification by mass spectrometry Nucleic acids research Medium 38224454
2025 The C-terminus of Zuo1 (residues 348-433; DNAJC2 yeast ortholog) interacts with G4-DNA structures; this interaction stabilizes the G4 structure and triggers conformational shifts depending on cation environment; Zuo1 targets a specific conformation state of G4-IX on yeast chromosome IX. NMR spectroscopy, single-molecule FRET (smFRET), in vivo G4 detection, domain truncation analysis Nucleic acids research Medium 41182900
2025 Zuo1 (DNAJC2 yeast ortholog) is a critical component of the signaling pathway that reduces protein synthesis upon mitochondrial dysfunction; deletion of ZUO1 largely prevents slow growth and reduced translation rates in tom70Δ/tom71Δ cells under heat stress, without rescuing mitochondrial defects, indicating a regulatory role for Zuo1 in muting translation in response to mitoprotein-induced stress. Genetic deletion (zuo1Δ, tom70Δ/tom71Δ), translation rate measurements, mitochondrial import assays, heat stress bioRxivpreprint Low bio_10.1101_2025.08.21.671487

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae. The EMBO journal 178 1396572
2001 RAC, a stable ribosome-associated complex in yeast formed by the DnaK-DnaJ homologs Ssz1p and zuotin. Proceedings of the National Academy of Sciences of the United States of America 177 11274393
1998 Zuotin, a ribosome-associated DnaJ molecular chaperone. The EMBO journal 138 9707440
2010 Transcriptional activation of polycomb-repressed genes by ZRF1. Nature 119 21179169
2005 The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex. Proceedings of the National Academy of Sciences of the United States of America 115 16002468
2005 The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1. Nature structural & molecular biology 105 15908962
2005 Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science (New York, N.Y.) 99 15802566
2021 p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation. Molecular cancer 60 34579723
2004 Activation of pleiotropic drug resistance by the J-protein and Hsp70-related proteins, Zuo1 and Ssz1. Molecular microbiology 39 15225326
2016 Dual interaction of the Hsp70 J-protein cochaperone Zuotin with the 40S and 60S ribosomal subunits. Nature structural & molecular biology 37 27669034
2000 A putative oncogenic role for MPP11 in head and neck squamous cell cancer. Cancer research 37 11034098
2017 DICER and ZRF1 contribute to chromatin decondensation during nucleotide excision repair. Nucleic acids research 35 28402505
2005 Broad sensitivity of Saccharomyces cerevisiae lacking ribosome-associated chaperone ssb or zuo1 to cations, including aminoglycosides. Eukaryotic cell 35 15643063
2012 ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. Oncogene 34 22733129
2012 Unfolding of the C-terminal domain of the J-protein Zuo1 releases autoinhibition and activates Pdr1-dependent transcription. Journal of molecular biology 34 23036859
2017 ZRF1 is a novel S6 kinase substrate that drives the senescence programme. The EMBO journal 33 28242756
2016 ZRF1 mediates remodeling of E3 ligases at DNA lesion sites during nucleotide excision repair. The Journal of cell biology 32 27091446
2011 Role for the molecular chaperones Zuo1 and Ssz1 in quorum sensing via activation of the transcription factor Pdr1. Proceedings of the National Academy of Sciences of the United States of America 31 22203981
2014 Zrf1 is required to establish and maintain neural progenitor identity. Genes & development 28 24449271
2020 Zuo1 supports G4 structure formation and directs repair toward nucleotide excision repair. Nature communications 27 32764578
2015 ZRF1: a novel epigenetic regulator of stem cell identity and cancer. Cell cycle (Georgetown, Tex.) 23 25665097
2014 Direct interaction between Id1 and Zrf1 controls neural differentiation of embryonic stem cells. EMBO reports 23 25361733
2013 ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia. Oncogene 23 24292673
2001 Fungal Zuotin proteins evolved from MIDA1-like factors by lineage-specific loss of MYB domains. Molecular biology and evolution 23 11420378
2015 A conserved domain important for association of eukaryotic J-protein co-chaperones Jjj1 and Zuo1 with the ribosome. Biochimica et biophysica acta 20 25639645
2018 Overexpression of ZRF1 is related to tumor malignant potential and a poor outcome of gastric carcinoma. Carcinogenesis 19 29228320
2014 Functional conservation and divergence of J-domain-containing ZUO1/ZRF orthologs throughout evolution. Planta 19 24659052
2023 UV-induced G4 DNA structures recruit ZRF1 which prevents UV-induced senescence. Nature communications 17 37872164
2020 Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases. Heliyon 17 32904265
2016 ZRF1 Chromatin Regulators Have Polycomb Silencing and Independent Roles in Development. Plant physiology 17 27630184
2011 The flip side of the coin: role of ZRF1 and histone H2A ubiquitination in transcriptional activation. Cell cycle (Georgetown, Tex.) 15 21311219
2016 Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades. Disease markers 11 27847402
2019 Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70. PloS one 10 31091298
2016 Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 27350366
1995 Cloning and chromosomal localization of a mouse cDNA with homology to the Saccharomyces cerevisiae gene zuotin. Genomics 9 8666407
2021 DNAJC2 is reversely regulated by miR‑627‑3p, promoting the proliferation of colorectal cancer. Molecular medicine reports 8 34165158
1997 Sequence analysis of a near-subtelomeric 35.4 kb DNA segment on the right arm of chromosome VII from Saccharomyces cerevisiae carrying the MAL1 locus reveals 15 complete open reading frames, including ZUO1, BGL2 and BIO2 genes and an ABC transporter gene. Yeast (Chichester, England) 8 9090054
2019 DNAJC2 is required for mouse early embryonic development. Biochemical and biophysical research communications 7 31230751
2018 Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance. Oncotarget 7 29983888
2010 Identification of a novel peptide derived from the M-phase phosphoprotein 11 (MPP11) leukemic antigen recognized by human CD8+ cytotoxic T lymphocytes. Hematology/oncology and stem cell therapy 7 20231810
2023 The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition. The EMBO journal 6 37984430
2021 A Novel Epigenetic Regulator ZRF1: Insight into Its Functions in Plants. Genes 6 34440419
2016 Zrf1 controls mesoderm lineage genes and cardiomyocyte differentiation. Cell cycle (Georgetown, Tex.) 4 27754813
2006 Zuotin, a DnaJ molecular chaperone, stimulates cap-independent translation in yeast. Biochemical and biophysical research communications 4 17027912
2024 NAC and Zuotin/Hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo. Nucleic acids research 3 38224454
2023 Zuo1, a ribosome-associated J protein, is involved in glucose repression in Saccharomyces cerevisiae. FEMS yeast research 2 37550218
2025 The epigenetic factor Zrf1 regulates intestinal stem cell proliferation during midgut regeneration. PLoS genetics 0 41144510
2025 The Zuo1 C-terminal domain stabilizes DNA guanosine quadruplex (G4) structures located on Chromosome IX in Saccharomyces cerevisiae. Nucleic acids research 0 41182900

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