Affinage

DNAJC2

DnaJ homolog subfamily C member 2 · UniProt Q99543

Length
621 aa
Mass
72.0 kDa
Annotated
2026-04-28
50 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAJC2 (also known as ZRF1/MPP11/Zuotin) is a multifunctional J-domain protein that operates at the intersection of cotranslational protein folding, chromatin regulation, DNA repair, and cellular senescence. On the ribosome, DNAJC2 forms the ribosome-associated complex (RAC) with the atypical Hsp70 Ssz1/Hsp70L1, stimulating the ATPase activity of the canonical Hsp70 Ssb/Hsc70 to promote nascent polypeptide folding; it contacts both the 60S subunit near the polypeptide exit tunnel and the 40S subunit via its C-terminal four-helix bundle, and perturbation of these contacts alters translational fidelity and stress-responsive translational output (PMID:9707440, PMID:11274393, PMID:16002468, PMID:27669034, PMID:37984430). In the nucleus, DNAJC2 binds monoubiquitinated histone H2A (H2A-ubK119) through an ubiquitin-interacting motif within its zuotin homology domain, displacing PRC1 to activate polycomb-repressed developmental genes including INK4-ARF locus targets, and it directly interacts with RARα to regulate retinoic acid-responsive transcription (PMID:21179169, PMID:22733129, PMID:24292673). DNAJC2 also participates in nucleotide excision repair by remodeling E3 ligase complexes at UV lesion sites, recruiting DICER for chromatin decondensation, and stabilizing G-quadruplex DNA structures that direct repair pathway choice; phosphorylation of DNAJC2 at Ser47 by mTORC1-S6 kinases drives p16-dependent cellular senescence (PMID:27091446, PMID:32764578, PMID:37872164, PMID:28242756). Knockout of Dnajc2 in mice causes early post-implantation lethality, underscoring its essential role in mammalian development (PMID:31230751).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    Identifying the founding member of the zuotin family as a Z-DNA binding protein established that this gene product could interact with non-B-form nucleic acid structures, an activity whose biological significance would only become clear decades later.

    Evidence Southwestern blot and Z-DNA binding assay with recombinant yeast Zuotin; ZUO1 gene disruption yielded slow-growth phenotype

    PMID:1396572

    Open questions at the time
    • Physiological relevance of Z-DNA binding was unclear
    • No connection to chaperone function yet established
  2. 1998 High

    Establishing that Zuotin is a ribosome-associated J-domain protein functioning with Hsp70 Ssb resolved the paradox of its DnaJ domain and connected it to cotranslational protein folding rather than DNA metabolism.

    Evidence Ribosome fractionation, RNA binding assays, and genetic epistasis (zuo1Δ phenocopies ssbΔ) in yeast

    PMID:9707440

    Open questions at the time
    • Identity of the direct Hsp70 partner on the ribosome was not resolved
    • Mechanism of ribosome tethering unknown
  3. 2001 High

    Discovery that Zuo1 forms a stable 1:1 ribosome-associated complex (RAC) with the Hsp70 Ssz1 defined the minimal functional chaperone unit at the ribosome and showed it could stimulate mitochondrial protein translocation in vitro.

    Evidence Co-purification, analytical ultracentrifugation, and in vitro translocation assay with reconstituted RAC

    PMID:11274393

    Open questions at the time
    • How RAC communicates with Ssb was not biochemically defined
    • Structural basis of ribosome attachment unknown
  4. 2005 High

    Three contemporaneous studies established that RAC is conserved in mammals (DNAJC2/MPP11 with Hsp70L1), that Zuo1's J-domain stimulates Ssb ATPase only in the context of the RAC complex, and that DNAJC2 can functionally substitute for yeast Zuo1, proving evolutionary conservation of ribosome-tethered chaperone systems.

    Evidence Mammalian RAC purification and mass spectrometry, yeast complementation, in vitro ATPase reconstitution with systematic Ssz1 mutagenesis

    PMID:15802566 PMID:15908962 PMID:16002468

    Open questions at the time
    • Structural basis of J-domain activation by Ssz1 was not determined
    • Substrate specificity of RAC on nascent chains was unknown
  5. 2004 High

    Demonstration that the C-terminal domain of Zuo1 activates transcription factor Pdr1 independently of ribosome association revealed a separable off-ribosome nuclear/transcriptional function, establishing DNAJC2 as a bifunctional protein.

    Evidence Domain deletions, PDR reporter assays, and ribosome dissociation experiments in yeast

    PMID:15225326

    Open questions at the time
    • How Zuo1 is released from ribosomes to execute transcriptional function was unknown
    • Direct physical interaction with Pdr1 not yet shown
  6. 2010 High

    The landmark discovery that ZRF1/DNAJC2 binds H2A-ubK119 through a ubiquitin-interacting domain within the zuotin homology domain and displaces PRC1 to activate polycomb-repressed genes fundamentally redefined the protein as a chromatin regulator in mammals.

    Evidence Reciprocal Co-IP, genome-wide ChIP-seq of ZRF1/RING1B/H2A-ub, domain mapping, and loss-of-function in differentiating human cells

    PMID:21179169

    Open questions at the time
    • Whether H2A-ub binding and ribosome association are mutually exclusive was not tested
    • Mechanism of selectivity for specific polycomb target genes was unclear
  7. 2012 High

    Connecting ZRF1 to the INK4-ARF locus showed that its PRC1-displacing activity directly controls oncogene-induced senescence, while structural resolution of the yeast C-terminal four-helix bundle explained the autoinhibitory mechanism governing the off-ribosome transcriptional function.

    Evidence ChIP at INK4-ARF promoters upon oncogenic Ras expression with ZRF1 depletion/rescue; NMR structure of Zuo1 C-terminal domain with functional mutagenesis

    PMID:22733129 PMID:23036859

    Open questions at the time
    • Whether senescence function requires H2A-ub binding was not directly tested
    • Post-translational modifications controlling the autoinhibitory bundle opening were unknown
  8. 2014 High

    Studies in ESC-derived neural progenitors and embryonic cortex established that Zrf1 is required for neural fate specification by activating Wnt ligand expression, and that the BHLh factor Id1 sequesters Zrf1 off chromatin to maintain pluripotency, revealing an upstream regulatory mechanism.

    Evidence Zrf1 knockdown in ESC-derived NPCs, in vivo cortical depletion, Wnt rescue; Co-IP of Id1-Zrf1, ChIP, epistasis in Id1-KO ESCs

    PMID:24449271 PMID:25361733

    Open questions at the time
    • Whether Id1-Zrf1 interaction is direct or bridged by chromatin was not fully resolved
    • Connection to ribosome-associated function during differentiation was not addressed
  9. 2016 High

    Cryo-EM and in vivo cross-linking revealed that Zuo1 simultaneously contacts both ribosomal subunits — J-domain at the 60S exit tunnel and C-terminal four-helix bundle at 40S ES12 — and that these contacts govern translational fidelity (stop-codon readthrough and frameshifting).

    Evidence Cryo-EM structure, site-specific in vivo cross-linking, ES12 deletion mutants, frameshifting/readthrough reporters in yeast

    PMID:27669034

    Open questions at the time
    • Mechanism by which 40S contact modulates decoding center fidelity was not resolved
    • Whether mammalian DNAJC2 contacts 40S equivalently was not tested
  10. 2016 High

    Discovery that ZRF1 remodels E3 ligase complexes at UV lesion sites — displacing UV-RING1B and assembling UV-DDB-CUL4A — established a direct role in global-genome nucleotide excision repair, extending its H2A-ub reading activity to the DNA damage response.

    Evidence Co-IP, ChIP at UV lesion sites, NER repair assays, epistasis with XPC in human cells

    PMID:27091446

    Open questions at the time
    • Whether ZRF1's NER role is independent of its developmental PRC1-displacement function was not separated
    • Structural basis of E3 ligase complex remodeling was unknown
  11. 2017 High

    Two discoveries linked DNAJC2 to distinct signaling axes: mTORC1-S6 kinase phosphorylation of ZRF1 at Ser47 drives p16-dependent senescence, and ZRF1 recruits DICER to UV-damaged chromatin for PARP1-dependent decondensation during NER.

    Evidence Chemical genetic S6K substrate screen, in vitro kinase assay, phospho-mutant rescue for senescence; ZRF1-DICER Co-IP, ChIP at UV sites, nuclease-dead DICER rescue for NER

    PMID:28242756 PMID:28402505

    Open questions at the time
    • Whether Ser47 phosphorylation affects chromatin binding or ribosome association was not tested
    • DICER recruitment mechanism to ZRF1 was not structurally defined
  12. 2020 High

    Identification of Zuo1/ZRF1 as a G-quadruplex DNA binding protein that stabilizes G4 structures in vivo and recruits NER factors revealed a new nucleic acid recognition activity that directs DNA repair pathway choice at structured DNA.

    Evidence G4 pull-down in vitro, G4-specific immunostaining in vivo, UV sensitivity assays, NER factor recruitment, genetic epistasis with NER mutants in yeast

    PMID:32764578

    Open questions at the time
    • Which domain of Zuo1 contacts G4 DNA was not mapped
    • Whether mammalian ZRF1 also binds G4s was not shown
  13. 2023 High

    Follow-up work showed that UV irradiation induces nuclear G4 accumulation that recruits ZRF1, and that ZRF1 loss leads to unresolved G4s, defective UV repair, and DDB2-driven senescence — connecting G4 biology, NER, and senescence into a unified ZRF1-dependent pathway. Concurrently, RAC/Ssb was shown to be essential for translational downregulation and autophagy upon TORC1 inhibition.

    Evidence G4 immunostaining after UV, ZRF1 ChIP at G4 sites, DDB2 expression analysis, senescence assays in human cells; polysome profiling and autophagy assays after rapamycin treatment in yeast zuo1Δ

    PMID:37872164 PMID:37984430

    Open questions at the time
    • Molecular mechanism linking G4 binding to NER factor recruitment was not resolved
    • Whether TORC1-responsive translation and senescence functions are mechanistically linked was not tested
  14. 2025 High

    NMR and single-molecule FRET mapped the G4 binding activity to the C-terminus of Zuo1 (residues 348–433) and showed it stabilizes and remodels G4 topology in a cation-dependent manner, providing the first structural view of how zuotin recognizes non-B-form DNA.

    Evidence NMR spectroscopy, smFRET of G4-Zuo1 interactions, C-terminal deletion mutants in vivo

    PMID:41182900

    Open questions at the time
    • Whether G4 binding competes with ribosome association (both via C-terminus) was not addressed
    • Structural model of the G4-Zuo1 complex at atomic resolution is lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DNAJC2 partitions between its ribosome-associated chaperone function and its nuclear chromatin/DNA repair functions — whether this is regulated by post-translational modification, cell cycle, or differentiation state — remains a central unresolved question.
  • No mechanism for ribosome-to-nucleus shuttling or partitioning has been identified
  • Whether G4 binding, H2A-ub binding, and ribosome attachment are mutually exclusive or sequential is untested
  • Structural basis of the full-length mammalian DNAJC2 on the ribosome has not been determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0042393 histone binding 3 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005840 ribosome 5 GO:0005694 chromosome 4 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-73894 DNA Repair 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9612973 Autophagy 1
Partners
BRD4DICER1HSPA14ID1PARP1RARARING1RNF2
Complex memberships
Ribosome-associated complex (RAC)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Zuotin (yeast ortholog of DNAJC2/ZRF1) was identified as a Z-DNA binding protein; the ZUO1 gene was cloned and the expressed protein showed Z-DNA binding activity. Disruption of ZUO1 resulted in a slow growth phenotype. Z-DNA binding assay, Southwestern blot, gene cloning, expression in E. coli, ZUO1 disruption The EMBO journal High 1396572
1998 Zuotin (Zuo1) is a ribosome-associated DnaJ protein that functions with the Hsp70 Ssb on the ribosome to promote nascent polypeptide folding; ribosome association correlates with RNA binding activity. Cells lacking Zuo1 phenocopy cells lacking Ssb (cold sensitivity, aminoglycoside sensitivity, osmosensitivity). Deletion and truncation mutants, ribosome fractionation, RNA binding assay, genetic phenotypic analysis The EMBO journal High 9707440
2001 Zuo1 (yeast DNAJC2 ortholog) forms a stable 1:1 ribosome-associated complex (RAC) with the Hsp70 homolog Ssz1p. RAC is bound to the ribosome via the Zuo1/zuotin subunit. In vitro, RAC stimulates translocation of a ribosome-bound mitochondrial precursor protein into mitochondria. Deletion of either RAC subunit causes a similar phenotype in vivo. Co-purification, analytical ultracentrifugation, in vitro translocation assay, genetic deletion Proceedings of the National Academy of Sciences of the United States of America High 11274393
2005 Human MPP11 (DNAJC2) is localized to the cytosol and associates with ribosomes. It forms a stable complex with Hsp70L1 (the mammalian Ssz1 homolog), constituting the mammalian ribosome-associated complex (RAC). This mammalian RAC is functional in yeast complementation experiments. Subcellular fractionation, ribosome sedimentation, co-purification/mass spectrometry, yeast complementation Proceedings of the National Academy of Sciences of the United States of America High 16002468
2005 Human Mpp11 (DNAJC2) is a ribosome-associated J protein that partners with the soluble Hsc70 (mammalian Ssa homolog) when expressed in yeast, partially substituting for yeast Zuo1. This establishes that ribosome-tethered molecular chaperones are conserved across eukaryotes. Yeast complementation, ribosome association assay, genetic rescue Science (New York, N.Y.) High 15802566
2005 The ribosome-associated J-protein Zuo1 is the obligate partner of the Hsp70 Ssb. Zuo1 efficiently stimulates Ssb ATPase activity only when in complex with another Hsp70, Ssz1. Ssz1 binds ATP but nucleotide binding/hydrolysis is not required for its in vivo function; Ssz1's primary role is to facilitate Zuo1's J-protein activity toward Ssb. ATPase stimulation assay, in vitro biochemical reconstitution, active-site mutagenesis of Ssz1 (11 substitutions), in vivo functional analysis Nature structural & molecular biology High 15908962
2004 The C-terminal domain of Zuo1 (not required for ribosome chaperone function) is necessary and sufficient for activating the transcription factor Pdr1 and inducing pleiotropic drug resistance (PDR). The N-terminal ATPase domain of Ssz1 is sufficient for PDR induction. Ssz1 and Zuo1 must be free of ribosomes to induce PDR, distinguishing this function from their chaperone role. Domain deletion analysis, overexpression studies, PDR reporter assay, ribosome dissociation experiments Molecular microbiology High 15225326
2010 ZRF1 (DNAJC2) is specifically recruited to histone H2A monoubiquitinated at Lys 119 (H2A-ubK119) via a novel ubiquitin-interacting domain located within the evolutionarily conserved zuotin domain. At the onset of differentiation, ZRF1 displaces PRC1 from chromatin and facilitates transcriptional activation of polycomb-repressed genes. Co-immunoprecipitation, genome-wide ChIP-seq mapping of ZRF1/RING1B/H2A-ubiquitin, domain mapping, loss-of-function in human cell lines Nature High 21179169
2011 ZRF1 displaces PRC1 from chromatin in a two-step mechanism: first displacing PRC1 and then acting with H2A-specific deubiquitinases to facilitate transcriptional activation. This dual role of the H2A ubiquitin mark (silencing vs. activation platform) was established. Co-immunoprecipitation, chromatin fractionation, deubiquitinase functional assays in human cell lines Cell cycle (Georgetown, Tex.) Medium 21311219
2012 ZRF1 controls oncogene-induced senescence by binding to the p15INK4b, ARF and p16INK4a promoters following oncogenic Ras expression; ZRF1 depletion bypasses senescence by preventing Arf and p16Ink4a expression, establishing ZRF1 as a regulator of the INK4-ARF locus. ZRF1 depletion (siRNA/shRNA), ChIP at INK4-ARF promoters, senescence assays, rescue experiments in oncogenic Ras-expressing cells Oncogene High 22733129
2012 The C-terminal 13 residues of Zuo1 directly activate Pdr1 transcription factor via a hydrophobic interaction; these residues are sequestered in an autoinhibitory left-handed four-helix bundle. Unfolding of this bundle is required for Pdr1 activation and is accompanied by ribosome dissociation. NMR structure determination of C-terminal domain, two-hybrid interaction mapping, truncation and point mutant analysis, PDR reporter assays Journal of molecular biology High 23036859
2011 Zuo1 and Ssz1 activate Pdr1 transcription factor leading to premature growth arrest at the diauxic shift; they modulate quorum sensing via Pdr1-target membrane transporters Pdr5 and Snq2. Direct two-hybrid interactions between Pdr1 and both Zuo1 and Ssz1 were demonstrated. Yeast two-hybrid, deletion mutant growth assays, conditioned medium experiments, PDR reporter assays Proceedings of the National Academy of Sciences of the United States of America Medium 22203981
2013 ZRF1 controls the retinoic acid (RA)-regulated gene network through direct interaction with RARα; ZRF1 binds to RA target genes and regulates approximately half of RA target gene transcription. ZRF1 depletion reduces proliferation, induces apoptosis, and enhances differentiation in AML cells, and suppresses leukemia in a xenograft model. Co-immunoprecipitation (ZRF1-RARα), ChIP-seq, genome-wide expression profiling, siRNA knockdown, xenograft mouse model Oncogene High 24292673
2014 Zrf1 is required for NPC specification from ESCs and promotes expression of NPC markers including Pax6. Zrf1 is essential for establishing Wnt ligand expression levels needed for NPC self-renewal. Reactivation of Wnt signaling rescues Pax6 expression in Zrf1-depleted NPCs. Zrf1 knockdown in ESC-derived NPCs, in vivo depletion in embryonic cortex, Wnt rescue experiments, gene expression analysis Genes & development High 24449271
2014 Id1 directly interacts with Zrf1 and blocks Zrf1 recruitment to chromatin in ESCs, preventing activation of neural genes. Upon differentiation, decreased Id1 expression allows Zrf1 binding to neural gene loci. Zrf1 depletion rescues polycomb target expression up-regulated in Id1-knockout ESCs, placing Zrf1 downstream of Id1 in neural fate specification. Co-immunoprecipitation (Id1-Zrf1), ChIP, siRNA knockdown, Id1-KO ESC rescue experiments EMBO reports High 25361733
2015 The zuotin homology domain (ZHD), conserved between Zuo1 and Jjj1, is important for ribosome association of both J proteins. The ZHD of Zuo1 and Jjj1 bind overlapping sites on ribosomes. The N-terminal segment of Jjj1 (J-domain + ZHD) is sufficient to rescue cold- and cation-sensitivity of Δzuo1 cells. Deletion analysis, ribosome fractionation, growth assays, genetic complementation Biochimica et biophysica acta Medium 25639645
2016 ZRF1 mediates remodeling of E3 ligase complexes at UV DNA lesion sites during GG-NER: ZRF1, via its H2A-ubiquitin binding activity, causes displacement of the UV-RING1B E3 ligase complex and assembly of the UV-DDB-CUL4A complex. ZRF1 is essential for GG-NER and its function is linked to the damage recognition factor XPC. Co-immunoprecipitation, ChIP at UV lesion sites, siRNA depletion, NER repair assays, epistasis with XPC The Journal of cell biology High 27091446
2016 Zuo1 interacts with both the 40S and 60S ribosomal subunits: the J-domain region contacts the 60S near the polypeptide exit site (interacting with eL31 and 25S rRNA helix 24), and the C-terminal 4-helix bundle region interacts with 18S rRNA expansion segment 12 (ES12) of the 40S. Deletions in ES12 or the Zuo1 C-terminus alter stop-codon readthrough and -1 frameshifting. Cryo-EM structural analysis, in vivo site-specific cross-linking, deletion mutants, frameshifting/readthrough reporter assays Nature structural & molecular biology High 27669034
2017 ZRF1 is phosphorylated on Ser47 by S6 kinases (downstream of mTORC1) both in cultured cells and in mammalian tissues in vivo. This phosphorylation drives a senescence programme; knockdown of ZRF1 or expression of a phosphorylation-resistant S47A mutant blunts S6 kinase-dependent senescence and alters p16 levels. Chemical genetic screen for S6K substrates, in vitro kinase assay, phospho-specific analysis in vivo, ZRF1 knockdown and phospho-mutant expression The EMBO journal High 28242756
2017 DICER is recruited to chromatin at UV-damaged sites in a ZRF1-dependent manner. ZRF1 and DICER together impact chromatin conformation via PARP1 to promote chromatin decondensation during NER. DICER's role in chromatin decondensation is independent of its catalytic (endonuclease) activity. Co-immunoprecipitation (ZRF1-DICER), ChIP upon UV irradiation, PARP1 functional assays, catalytic mutant analysis, nuclease-dead DICER rescue Nucleic acids research Medium 28402505
2019 The 4-helix bundle (4HB) domain of human DNAJC2/ZRF1 also forms a four-helix bundle as in yeast, with conserved positive charge in Helix I for 40S interaction. The C-terminal extension of the human 4HB serves as a linker to SANT domains (absent in fungi). In yeast, the C-terminal hydrophobic plug of the 4HB is required for bundle stability and off-ribosome transcriptional activation function. NMR structure determination of human and yeast 4HB domains, evolutionary sequence analysis, positive selection analysis, functional mutagenesis PloS one High 31091298
2019 DNAJC2/ZRF1 is required for early mouse embryonic development; knockout of Dnajc2 in FVB/Nj mice causes early post-implantation lethality. Maternal Dnajc2 mRNA allows preimplantation development but is insufficient for post-implantation. CRISPR/Cas9 knockout in mice, siRNA knockdown of maternal mRNA in 1-cell embryos Biochemical and biophysical research communications Medium 31230751
2020 Zuo1 is a novel G-quadruplex (G4) DNA-binding protein in vitro and in vivo. In the absence of Zuo1, fewer G4 structures form in cells, growth slows, and cells become UV-sensitive. Zuo1 function at G4 structures recruits NER factors, promoting genome stability. In NER-deficient cells, G4 structures become accessible to translesion synthesis. G4 pull-down assay (in vitro), G4-specific immunostaining (in vivo), UV sensitivity assay, NER factor recruitment analysis, genetic epistasis with NER mutants Nature communications High 32764578
2021 ZRF1 interacts with BRD4 and the p113 isoform encoded by CUX1 circular RNA to form a transcriptional regulatory complex. This complex mediates transactivation of ALDH3A1, NDUFA1, and NDUFAF5, driving lipid metabolic reprogramming and mitochondrial activity in neuroblastoma. A peptide blocking p113-ZRF1 interaction suppresses tumorigenesis. Co-immunoprecipitation, mass spectrometry, ChIP-seq, RNA-seq, dual-luciferase reporter, inhibitory peptide blockade Molecular cancer Medium 34579723
2023 Upon UV irradiation, G4 DNA structures accumulate in cell nuclei and recruit ZRF1 to G4 sites. ZRF1 binding to G4s ensures genome stability and prevents UV-induced senescence. Loss of ZRF1 leads to G4 accumulation, defective UV lesion repair, and senescence driven by upregulation of DDB2. G4-specific immunostaining after UV irradiation, ZRF1 ChIP at G4 sites, siRNA ZRF1 depletion, senescence assays, DDB2 expression analysis Nature communications High 37872164
2023 The RAC/Ssb chaperone system (Zuo1 + Ssb) is required to maintain proteostasis and cell viability under TORC1 inhibition in yeast. Zuo1-Ssb functional interaction is required for translational downregulation upon TORC1 inhibition. In zuo1Δ cells, autophagy is defective, preventing eIF4G degradation after TORC1 inhibition. TORC1 inhibition (rapamycin), polysome profiling, eIF4G degradation assays, autophagy assays, genetic deletion of ZUO1/SSB The EMBO journal Medium 37984430
2024 NAC and Zuotin/Hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo. In vivo cross-linking shows NAC and Zuotin can interact at the ribosome simultaneously. When both are present, NAC is modestly shifted from its exclusive position seen by cryo-EM. Hsp70 can still 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, translation initiation inhibition controls, comparison with cryo-EM structural data Nucleic acids research Medium 38224454
2025 The C-terminus of Zuo1 (residues 348–433) directly interacts with G4 DNA structures. This interaction stabilizes G4 topology and triggers conformational shifts in G4s depending on the cation environment; Zuo1 targets a specific conformation state of G4 IX on yeast chromosome IX. NMR spectroscopy, single-molecule FRET (smFRET), in vivo G4 experiments with C-terminal deletion mutants Nucleic acids research High 41182900
2025 Zuo1 is a critical component of the signaling pathway that reduces protein synthesis (mutes translation) upon mitochondrial dysfunction in yeast. Deletion of ZUO1 prevents the slow growth and reduced translation rates caused by Tom70/Tom71 deletion under heat stress, while worsening mitochondrial defects, establishing RAC as a stress-controlled regulatory element of cytosolic translation machinery. Genetic deletion of ZUO1 in tom70Δ/tom71Δ background, polysome profiling, growth assays under heat stress bioRxivpreprint Medium bio_10.1101_2025.08.21.671487

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
1992 Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae. The EMBO journal 176 1396572
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 58 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
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
2014 Direct interaction between Id1 and Zrf1 controls neural differentiation of embryonic stem cells. EMBO reports 22 25361733
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
2016 ZRF1 Chromatin Regulators Have Polycomb Silencing and Independent Roles in Development. Plant physiology 17 27630184
2020 Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases. Heliyon 16 32904265
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
2016 Arabidopsis thaliana gonidialess A/Zuotin related factors (GlsA/ZRF) are essential for maintenance of meristem integrity. Plant molecular biology 7 26826012
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
2019 Arabidopsis ZUOTIN RELATED FACTOR1 Proteins Are Required for Proper Embryonic and Post-Embryonic Root Development. Frontiers in plant science 5 31824531
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