Affinage

YBX3

Y-box-binding protein 3 · UniProt P16989

Length
372 aa
Mass
40.1 kDa
Annotated
2026-06-11
100 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YBX3 (ZONAB/DbpA/CSDA) is a Y-box/cold-shock domain protein that operates as a density-regulated nucleocytoplasmic switch coupling epithelial junction status to both transcriptional control of proliferation/differentiation genes and post-transcriptional control of metabolic transporter mRNAs (PMID:12566432, PMID:20133480, PMID:31189097). In its cytoplasmic mode it is retained at tight junctions through the ZO protein system, where ZO-1 and ZO-2 act redundantly to control its junctional localization and protein stability; the retention is indirect, since full-length ZO-1 does not bind DbpA directly (PMID:12566432, PMID:24986862). Loss of junctional retention or its modulation by partners drives nuclear accumulation, where YBX3 binds promoters of proliferative and cell-cycle genes — PCNA and cyclin D1 — to promote G1/S progression in concert with CDK4, and represses differentiation programs by binding target promoters including megalin/cubilin and AML1/Runx1 (PMID:16508013, PMID:17158914, PMID:19328795, PMID:20133480). Its nuclear transcriptional output is gated by a network of interactors: RalA relieves YBX3-mediated transcriptional repression in a GTP-dependent manner, symplekin promotes nuclear accumulation and transcription, GEF-H1/Rho signaling drives nuclear entry, and Apg-2 competes with YBX3 for the ZO-1 SH3 domain (PMID:15592429, PMID:17158914, PMID:16407410, PMID:19730435). As a sequence-specific and structure-sensitive DNA-binding protein it also engages diverse promoter elements (PMID:8972186, PMID:1923758, PMID:15893750). In parallel, YBX3 functions as an mRNA-stabilizing RNA-binding protein that binds and stabilizes amino acid transporter transcripts (SLC7A5/SLC3A2, SLC1A5, Slc3a2) to govern intracellular amino acid supply, supporting proliferation, skeletal muscle differentiation, and brown-adipocyte thermogenesis (PMID:31189097, PMID:38159852, PMID:39481849). Its expression is driven by E2F1, linking it to cell-cycle entry (PMID:15313206).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 Medium

    Established the founding biochemical activity of human DbpA/YBX3 as a DNA-binding protein, defining it as a candidate chromatin/DNA-repair factor before any cellular role was known.

    Evidence Phage expression library screening and EMSA with double-stranded, single-stranded, and abasic DNA, varying Mg2+

    PMID:1923758

    Open questions at the time
    • No cellular function tied to the DNA-binding activity
    • Preference for depurinated DNA not validated in a repair pathway in vivo
  2. 1995 Medium

    Defined the gene structure and dual cytoplasmic/nuclear localization, hinting that YBX3 is a shuttling protein with serum-responsive expression.

    Evidence Genomic cloning, Northern blot, CAT reporter, and immunofluorescence

    PMID:7628487

    Open questions at the time
    • Signals controlling the cytoplasmic-vs-nuclear balance not identified
    • Perinuclear localization not mechanistically explained
  3. 1997 Medium

    Showed YBX3 is a sequence-specific transcriptional regulator that can both repress (grp78, antagonizing YY1) and activate (thymidine kinase CCAAT element) promoters, establishing context-dependent transcriptional roles.

    Evidence EMSA, cotransfection reporter assays, and yeast two-hybrid interaction trap

    PMID:8972186 PMID:9419421

    Open questions at the time
    • Determinants of activation vs repression not resolved
    • Endogenous target relevance not established
  4. 1999 Medium

    Identified a CDK-binding/inhibitory activity in the YBX3 C-terminus, an early link between YBX3 and cell-cycle kinase regulation.

    Evidence Yeast two-hybrid and in vitro kinase inhibition assays with Cdk5, Cdk4, Cdk2

    PMID:10100871

    Open questions at the time
    • In vitro inhibition not shown to operate in cells
    • Reconciliation with later pro-proliferative CDK4 cofactor role unaddressed
  5. 2003 High

    Defined the central regulatory paradigm: YBX3/ZONAB promotes proliferation via nuclear accumulation, with ZO-1 acting as a junctional sequestration brake and nuclear CDK4 as a downstream readout.

    Evidence RNAi/antisense and overexpression in MDCK cells, CDK4 co-IP, nuclear fractionation

    PMID:12566432

    Open questions at the time
    • Direct transcriptional targets not yet defined
    • Mechanism of ZO-1-dependent retention not molecularly resolved
  6. 2004 High

    Connected YBX3 to upstream oncogenic signaling and to its own expression control, showing RalA-GTP relieves YBX3 repression and E2F1 transactivates the YBX3 promoter.

    Evidence Reverse Ras recruitment Y2H, GTP-dependent co-IP and reporter assays; E2F1 overexpression with promoter deletion luciferase assays

    PMID:15313206 PMID:15592429

    Open questions at the time
    • Direct RalA-YBX3 contact interface not mapped
    • How RalA binding alters DNA occupancy unknown
  7. 2006 High

    Established the direct transcriptional mechanism for proliferation by identifying PCNA and cyclin D1 as YBX3 promoter targets and defined symplekin as a nuclear cofactor required for YBX3-dependent transcription.

    Evidence ChIP on PCNA/cyclin D1 promoters, microarray, RNAi, 3D MDCK morphogenesis; symplekin co-IP, recombinant reconstitution, and RNAi

    PMID:16508013 PMID:17158914

    Open questions at the time
    • How symplekin (a polyadenylation factor) supports transcription mechanistically unclear
    • Structure of the nuclear YBX3-symplekin complex unknown
  8. 2006 High

    Defined competitive regulation at the ZO-1 SH3 docking site, with Apg-2/Hsp110 antagonizing YBX3-ZO-1 association and modulating YBX3 transcriptional output and cell-cycle progression.

    Evidence ZO-1 SH3 domain library screening, co-IP, in vitro competition binding, reporter assays, regulated depletion in MDCK

    PMID:16407410

    Open questions at the time
    • Physiological signals regulating Apg-2 competition not defined
    • Reconciled later with indirect ZO-1 binding (idx 18)
  9. 2005 Medium

    Extended YBX3 transcriptional targeting to MUC1 and connected it to a glial gap-junction anchoring context, broadening the tissue and target repertoire.

    Evidence Southwestern/UV crosslinking and reporter assays on MUC1 -250 DHS; confocal colocalization and co-IP with ZO-1/connexins in mouse brain

    PMID:15893750 PMID:16045494

    Open questions at the time
    • Functional consequence of glial gap-junction association not tested
    • MUC1 regulation not validated in endogenous context
  10. 2009 High

    Established YBX3 as a Rho-pathway effector and a repressor of differentiation, linking GEF-H1/Rho-driven nuclear accumulation to cyclin D1 and showing symplekin/YBX3 represses AML1/Runx1 to block goblet-cell differentiation.

    Evidence Co-IP, nuclear fractionation, cyclin D1 reporter and RNAi; ChIP/EMSA on AML1 promoter with inducible knockdown and AML1-deficient mouse intestine

    PMID:19328795 PMID:19730435

    Open questions at the time
    • How Rho/GEF-H1 mechanistically triggers nuclear import unknown
    • Direct vs cofactor role at the AML1 promoter not fully separated
  11. 2010 High

    Demonstrated in vivo that YBX3 drives proliferation and suppresses epithelial differentiation, identifying megalin/cubilin as direct repression targets and showing EMT-like dysfunction upon dysregulation.

    Evidence Overexpression/RNAi, ChIP for megalin/cubilin in proximal tubule cells; lentiviral ZONAB/ZO-1 manipulation in mouse RPE with EM and angiography

    PMID:20133480 PMID:21209887

    Open questions at the time
    • Full differentiation gene network not mapped
    • EMT mechanism downstream of YBX3 not detailed
  12. 2014 High

    Clarified the upstream control and direct/indirect nature of junctional retention, placing CFTR-ZO-1 above the pathway and showing ZO-1/ZO-2 redundancy controls YBX3 stability rather than direct binding.

    Evidence CFTR co-IP/knockdown with cftr mouse models and reporters; combined ZO depletion, ZO-1 KO cells, MG132 rescue, and in vitro binding (negative)

    PMID:24986862 PMID:25107366

    Open questions at the time
    • The actual adaptor bridging YBX3 to junctions not identified
    • Mechanism of proteasomal stabilization by ZO proteins unresolved
  13. 2019 High

    Redefined YBX3 as an mRNA-stabilizing RNA-binding protein controlling amino acid homeostasis, identifying SLC7A5/SLC3A2 transporter mRNAs as direct targets.

    Evidence iCLIP RNA-binding mapping, mRNA stability assays, proteomics/transcriptomics integration, amino acid profiling after depletion

    PMID:31189097

    Open questions at the time
    • Sequence/structure determinants of target selection not defined
    • Relationship between RNA-binding and transcriptional modes within one cell unclear
  14. 2023 High

    Generalized the RNA-stabilization role across physiological programs, showing YBX3 stabilizes SLC1A5 to fuel skeletal muscle differentiation and acting in renal fibrosis via activated fibroblasts.

    Evidence RNAi, direct 3'UTR binding and reporter assays, amino acid profiling in muscle cells; Ybx3 KO mouse UUO model with RNAseq and ECM analysis

    PMID:37408260 PMID:38159852

    Open questions at the time
    • How YBX3 protein rises during differentiation independently of mRNA not explained
    • Fibroblast-specific YBX3 targets in fibrosis not defined
  15. 2024 High

    Established YBX3 as a metabolic regulator of thermogenesis by stabilizing Slc3a2 and Pparg mRNAs to support BCAA fueling in brown fat.

    Evidence BAT-specific AAV KD/OE in mice, mRNA stability assays, transcriptomics, metabolomics, mitochondrial stress tests

    PMID:39481849

    Open questions at the time
    • Whether the same RNA-binding mode operates in non-adipose tissues not tested here
    • Upstream control of YBX3 in BAT unknown
  16. 2023 Medium

    Showed non-coding RNAs reroute YBX3 localization and activity, with circSERPINE2 enforcing ZO-1 cytoplasmic sequestration and lncRNA BLACAT3 recruiting YBX3 to the nucleus to enhance NCF2/NF-κB.

    Evidence RNA pulldown+MS, RIP, ChIP on PCNA, p21/ubiquitin assays; MS identification of BLACAT3-YBX3 with in vitro/in vivo functional assays

    PMID:37612524 PMID:37831180

    Open questions at the time
    • Direct YBX3 transcriptional mechanism at NCF2 weakly validated (idx 28 Low confidence)
    • How RNA binding allosterically alters ZO-1 affinity unknown
  17. 2025 Medium

    Revealed YBX3 stability is itself a regulatory node and that YBX3 participates in transcriptional repression complexes, controlling ferroptosis via SLC7A11 and inflammatory genes via a CHK2-YBX1-YBX3 hub.

    Evidence USP5/YBX3 KO epistasis with organoid/xenograft and lysosomal degradation assays; IP-MS/phosphoproteomics, ChIP-seq, KO and YBX1 inhibitor in glioma

    PMID:40161682 PMID:41025501 PMID:41213937

    Open questions at the time
    • Direct vs indirect YBX3 effect on SLC7A11 stability not fully separated
    • Stoichiometry and DNA-targeting basis of the CHK2-YBX1-YBX3 complex unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single protein partitions between its junction-gated transcription-factor mode and its mRNA-stabilizing mode, and what molecular switch (post-translational modification, partner binding, or RNA association) governs that choice within a given cell.
  • No unified model linking DNA-binding and RNA-binding functions
  • Adaptor mediating indirect ZO-1 retention unidentified
  • No structural model of YBX3 in either nuclear or cytoplasmic complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1500931 Cell-Cell communication 3
Partners
APG-2CDK4GEF-H1RALASYMPLEKINYBX1ZO-1ZO-2
Complex memberships
CHK2-YBX1-YBX3 repressor hubZO-1 junctional complexsymplekin/ZONAB transcription complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ZONAB (YBX3) promotes epithelial cell proliferation and cell density by accumulating in the nucleus; ZO-1 sequesters ZONAB in the cytoplasm to restrict nuclear access and proliferation. ZONAB was found to associate with CDK4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4, indicating that ZONAB/ZO-1 regulate proliferation partly by controlling nuclear CDK4 accumulation. Antisense/RNAi knockdown of ZONAB in MDCK cells with proliferation assays; overexpression of ZO-1 or ZONAB; co-immunoprecipitation of ZONAB with CDK4; nuclear fractionation The Journal of cell biology High 12566432
2006 ZONAB (YBX3) transcriptionally regulates PCNA and cyclin D1 expression to drive G1/S-phase progression. ZONAB-responsive elements were identified in the PCNA and cyclin D1 promoters, and ZO-1 inhibits G1/S transition by cytoplasmic sequestration of a CDK4-ZONAB complex. cDNA microarray screening in MCF-10A cells with ZONAB overexpression; chromatin immunoprecipitation (ChIP) assays on PCNA and cyclin D1 promoters; RNAi knockdown; 3D cyst morphogenesis assay in MDCK cells Molecular and cellular biology High 16508013
2004 RalA (a Ras superfamily GTPase) interacts with ZONAB (YBX3) in a GTP-dependent manner. The RalA-ZONAB complex increases with epithelial cell density, and RalA interaction relieves transcriptional repression by ZONAB. Oncogenic Ras alleviates ZONAB-mediated transcriptional repression in a RalA-dependent manner. Reverse Ras recruitment yeast two-hybrid screen; co-immunoprecipitation; reporter gene (transcriptional repression) assays; cell density experiments The EMBO journal High 15592429
1997 Human dbpA (YBX3) and YB-1 (dbpB), both Y-box/cold shock domain proteins, bind the grp78 core promoter element (specifically the lower strand of the stress-inducible change region, SICR) and repress stress-inducible transcription. YBX3 can inhibit YY1 binding to the promoter and antagonizes YY1-mediated transcriptional activation. A yeast interaction trap identified YB-1 as a YY1-interacting protein. Expression library screening; gel shift (EMSA) assays; cotransfection reporter assays; yeast two-hybrid interaction trap Molecular and cellular biology Medium 8972186
1991 Human dbpA (YBX3) binds to double-stranded, single-stranded, and abasic (depurinated) DNA without strict sequence specificity. dbpA binds depurinated DNA more efficiently than undamaged DNA, and binding specificity is influenced by Mg2+, suggesting a role in chromatin maintenance or DNA repair. Phage expression library screening; electrophoretic mobility shift assay (EMSA); competition binding assays with Mg2+ variation Nucleic acids research Medium 1923758
1995 The human dbpA gene (YBX3) consists of 10 exons spanning ~24 kb; the cold-shock domain is encoded by exons 2–5. The promoter lacks a TATA box but contains an initiator consensus sequence and a serum-response element (SRE). dbpA protein localizes to both the cytoplasm and nucleus, particularly at the perinuclear region, by immunofluorescence. The dbpA gene maps to chromosome 12p13.1. Genomic cloning; Northern blot; transient CAT reporter assay; immunofluorescence; in situ hybridization European journal of biochemistry Medium 7628487
1997 dbpA (YBX3) binds the proximal CCAAT element (TKC1) of the human thymidine kinase (htk) promoter and overexpression of dbpA stimulates htk promoter activity via this element in a cell-cycle dependent manner. EMSA competition binding; cell transfection reporter assays; antigenic cross-reactivity assays Cell growth & differentiation Medium 9419421
1999 The C-terminal 172 amino acid domain of dbpA (YBX3) binds to Cdk5 in a yeast two-hybrid assay and strongly inhibits p35-activated Cdk5 kinase activity in vitro. This fragment also interacts with Cdk4 and inhibits Cdk4/cyclin D1 activity, but does not bind Cdk2 or inhibit Cdk2/cyclin A. Yeast two-hybrid screen of HeLa cDNA library; in vitro kinase inhibition assays FEBS letters Medium 10100871
2004 Transcription of dbpA (YBX3) is positively regulated by the transcription factor E2F1. An E2F-like binding sequence (-8 to -1 of the dbpA promoter) is required for E2F1-mediated transactivation, linking cell cycle entry signals to dbpA expression. E2F1 overexpression in Huh-7 cells; luciferase reporter assays with promoter deletion/mutation constructs Biochemical and biophysical research communications Medium 15313206
2005 In mouse brain, ZONAB (YBX3/MsY3) colocalizes with ZO-1 at oligodendrocyte and astrocyte gap junctions, associating specifically with oligodendrocytic Cx47 and Cx32 and astrocytic Cx43. This represents a functional context for ZONAB anchoring at glial gap junctions. Confocal immunofluorescence colocalization; co-immunoprecipitation of ZO-1 with connexins; pull-down assays The European journal of neuroscience Medium 16045494
2006 ZONAB/DbpA (YBX3) forms a complex with symplekin (an RNA polyadenylation/tight junction protein) that exists in the nucleus of kidney and intestinal epithelial cells. The interaction can be reconstituted with recombinant proteins. Symplekin depletion reduces nuclear ZONAB accumulation and transcriptional activity, and reduces cyclin D1 expression and proliferation, indicating that symplekin promotes ZONAB-dependent transcription. Co-immunoprecipitation; in vitro reconstitution with recombinant proteins; RNAi depletion of symplekin; reporter gene assays; cyclin D1 expression analysis Journal of cell science High 17158914
2006 Apg-2 (an Hsp110/Hsp70 subfamily heat shock protein) binds the SH3 domain of ZO-1 and competes with ZONAB (YBX3) for this binding site in vitro. Apg-2 co-immunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Apg-2 depletion inhibits G1/S phase progression, and Apg-2 regulates ZONAB's transcriptional activity in reporter assays, acting as a modulator of ZO-1-ZONAB signaling. cDNA library expression screening with ZO-1 SH3 domain fusion protein; co-immunoprecipitation; in vitro competition binding; reporter gene assays; regulated depletion in MDCK cells Molecular biology of the cell High 16407410
2009 ZONAB/DbpA (YBX3) associates with GEF-H1/Lfc (a RhoA GEF and tight junction-associated protein) and mediates Rho-stimulated transcription. GEF-H1 overexpression drives nuclear accumulation of ZONAB and activates transcription. Both GEF-H1 and ZONAB are required for endogenous cyclin D1 expression, and GEF-H1-stimulated cyclin D1 promoter activity requires ZONAB. Co-immunoprecipitation; overexpression studies; nuclear fractionation; cyclin D1 promoter reporter assays; RNAi knockdown EMBO reports High 19730435
2009 The symplekin/ZONAB (YBX3) complex represses intestinal goblet cell differentiation by suppressing expression of AML1/Runx1. Down-regulation of symplekin or ZONAB induces de novo AML1/Runx1 expression, which increases KLF4 expression and promotes goblet cell differentiation. ZONAB/DbpA was shown by ChIP to bind the AML1 promoter. Inducible shRNA knockdown of symplekin; siRNA knockdown of ZONAB/DbpA; ChIP assays; EMSA; differentiation marker analysis; AML1-deficient mouse intestine analysis Gastroenterology High 19328795
2010 ZONAB (YBX3) promotes proliferation and represses differentiation of proximal tubule epithelial cells. ZONAB overexpression increases PCNA and represses megalin and cubilin expression. ChIP demonstrated that megalin and cubilin are direct ZONAB target genes. Nuclear ZONAB levels are regulated by cell density and tight junction contact status. ZONAB overexpression; RNAi knockdown; reporter gene assays; chromatin immunoprecipitation (ChIP); differentiation marker analysis; cell density experiments Journal of the American Society of Nephrology High 20133480
2010 In the retinal pigment epithelium (RPE) in vivo, overexpression of ZONAB (YBX3) or knockdown of ZO-1 increases RPE proliferation and induces an epithelial-mesenchymal transition (EMT)-like phenotype with ultrastructural disorganization and RPE dysfunction. Lentiviral overexpression of ZONAB or shRNA knockdown of ZO-1 in mouse RPE in vivo; electron microscopy; fluorescein angiography; EMT marker analysis PloS one Medium 21209887
2007 Phosphatidylethanol (produced from ethanol by phospholipase D) accumulation induces claudin-1 endocytosis, disrupts the claudin-1/ZO-1 association, and triggers nuclear translocation of ZONAB (YBX3). The resulting nuclear ZONAB mediates the increase in intestinal cell density induced by chronic ethanol exposure. In vivo, phosphatidylethanol incorporation and nuclear ZONAB translocation correlated with increased proliferation in colonic epithelium. Phosphatidylethanol treatment of intestinal cells lacking alcohol dehydrogenase; claudin-1 endocytosis and co-IP assays; nuclear fractionation of ZONAB; in vivo ethanol-fed mouse model with colonic tissue analysis Molecular cancer research Medium 18025260
2014 CFTR interacts with ZO-1 through the CFTR PDZ-binding domain and regulates tight junction assembly and epithelial cell differentiation via the ZO-1-ZONAB (YBX3) pathway. CFTR inhibition or knockdown reduces ZO-1 expression and induces nuclear translocation of ZONAB, which upregulates CCND1 transcription and downregulates ErbB2 transcription. Cftr-deficient mice show increased nuclear ZONAB and decreased epithelial differentiation. Co-immunoprecipitation; CFTR knockdown/inhibition; 3D epithelial culture tubulogenesis model; reporter gene assays; cftr-/- and cftr-ΔF508 mouse tissue analysis Journal of cell science High 25107366
2014 ZO proteins (ZO-1, ZO-2, ZO-3) redundantly control the junctional retention and stability of DbpA/ZONAB (YBX3); depletion of ZO-1 alone has no effect, but combined depletion of ZO-1 and ZO-2 reduces junctional DbpA localization and protein stability (rescued by proteasome inhibitor MG132). In vitro binding assays showed full-length ZO-1 does not directly interact with DbpA, indicating that junctional retention involves indirect mechanisms. Depletion of individual and combined ZO proteins by RNAi; ZO-1 knockout (Eph4) cells; proteasome inhibition rescue; in vitro binding assays; nuclear fractionation; subcellular localization analysis The Journal of biological chemistry High 24986862
2019 YBX3 (YBX3) functions as an RNA-binding protein that stabilizes the mRNAs of the amino acid transporter genes SLC7A5 and SLC3A2, thereby controlling intracellular levels of SLC7A5/SLC3A2 amino acid substrates. Integration of proteomics, transcriptomics, and RNA-binding site analysis identified YBX3 as directly binding and stabilizing these SLC mRNAs. YBX3 depletion with proteomics and transcriptomics integration; RNA-binding site mapping (iCLIP); mRNA stability assays; amino acid profiling after YBX3 depletion Cell reports High 31189097
2005 DbpA/ZONAB (YBX3) binds DNase I hypersensitive site -250 of the human MUC1 mucin gene promoter, as identified by Southwestern blotting and UV cross-linking. Exogenous DbpA expression in COS-7 cells upregulates MUC1 promoter activity via this -250 DHS, establishing DbpA as a positive regulator of MUC1 transcription. Expression library screening with -250FP1 probe; Southwestern blotting; UV cross-linking; COS-7 cell transfection reporter assays Experimental cell research Medium 15893750
2018 Hypoxia-induced miR-191 suppresses ZONAB (YBX3) expression and its downstream target Cyclin D1, leading to G0/G1 cell cycle arrest and cell death in hepatic ischemia/reperfusion injury. ZONAB overexpression rescues the cell cycle arrest and apoptosis caused by miR-191. HIF-1α binds the miR-191 promoter to activate its expression, establishing a HIF-1α/miR-191/ZONAB signaling axis. miR-191 overexpression/knockout (CRISPR/Cas9 global KO mice); luciferase assays for HIF-1α binding to miR-191 promoter; ZONAB overexpression rescue experiments; mouse hepatic IRI model; cell cycle and apoptosis assays Cell death and differentiation Medium 29769640
2015 Bradykinin increases blood-tumor barrier (BTB) permeability via a NOS/NO/ZONAB pathway: bradykinin increases eNOS and nNOS expression and promotes nuclear translocation of ZONAB (YBX3), which then binds the promoters of claudin-5 and occludin (verified by ChIP), downregulating their expression and increasing BTB permeability. Bradykinin treatment of BTB cells; NOS inhibitors (l-NAME, 7-NI); ZONAB overexpression; chromatin immunoprecipitation (ChIP) for claudin-5 and occludin promoters Biochemical and biophysical research communications Medium 26106824
2010 CSDA/DbpA (YBX3) overexpression in a mouse squamous cell carcinoma model inhibits tumor growth and lymph node metastasis, and significantly reduces production of VEGF-A and VEGF-C, directly binding the hypoxia response element (HRE) and serum response element (SRE) to repress their transcription. CSDA expression plasmid transfection in NR-S1M cells; in vivo mouse SCC model; VEGF-A and VEGF-C expression analysis; promoter binding assays Clinical & experimental metastasis Medium 20623179
2012 CSDA (YBX3) physically interacts with Egr1 mRNA and posttranscriptionally stabilizes it (via a CSD element in the 3' UTR), thereby enabling GnRH-regulated EGR1 accumulation and maximal Lhb transcription in gonadotrophs. RNA-binding assay (CSDA-Egr1 mRNA interaction); siRNA depletion of endogenous Csda; chimeric luciferase reporter with Egr1 3' UTR; transient expression studies in LbetaT2/alphaT3 cells Biology of reproduction Medium 22053098
2020 YBX3 restricts influenza A virus (IAV) replication by interacting with the viral ribonucleoprotein (vRNP) complex. YBX3 overexpression inhibited virus replication, viral protein expression, and vRNA synthesis, while YBX3 knockdown increased virus growth and augmented nuclear NP accumulation and primary transcription. YBX3 was identified as a host factor interacting with vRNP by Strep-tag affinity purification coupled with mass spectrometry. Strep-tag affinity purification + mass spectrometry of vRNP from infected cells; YBX3 overexpression and RNAi knockdown; viral replication/transcription assays; nuclear NP accumulation analysis The Journal of general virology Medium 32553055
2023 YBX3 (YBX3) posttranscriptionally controls SLC1A5 amino acid transporter mRNA in skeletal muscle cells by directly binding the SLC1A5 3' UTR. YBX3 depletion reduces SLC1A5 expression, specifically decreases SLC1A5-transported intracellular amino acids, reduces cell proliferation, and impairs differentiation. YBX3 and SLC1A5 protein levels both increase substantially during skeletal muscle differentiation independently of their mRNA levels. YBX3 depletion by RNAi; direct YBX3-SLC1A5 mRNA binding assays; 3' UTR reporter assays; intracellular amino acid profiling; proliferation and differentiation assays in mouse skeletal muscle cells The Journal of biological chemistry High 38159852
2023 circSERPINE2 interacts with YBX3 (identified by RNA pulldown + mass spectrometry) and increases YBX3 affinity for ZO-1, causing cytoplasmic sequestration of YBX3. This prevents YBX3 from binding the PCNA promoter, inhibiting PCNA transcription and impairing p21 ubiquitin-mediated degradation, thus promoting mesenchymal stem cell senescence. RNA pulldown + mass spectrometry (circSERPINE2-YBX3); RIP assay; circSERPINE2 siRNA/overexpression; YBX3 ChIP on PCNA promoter; p21/ubiquitin assays; in vivo intra-articular injection Cellular and molecular life sciences Medium 37831180
2023 YBX3 mediates bladder cancer angiogenesis and metastasis by being recruited to the nucleus by lncRNA BLACAT3, where it synergistically enhances NCF2 transcription, activating downstream NF-κB signaling. m6A modification stabilizes BLACAT3, which recruits YBX3 as its nuclear shuttling partner. Mass spectrometry identification of BLACAT3-interacting proteins; RNA-seq; functional assays in vitro and in vivo; mechanistic analysis of NCF2 transcription by YBX3 Oncogene Low 37612524
2023 DbpA (YBX3) plays a role in renal fibrosis and kidney disease: DbpA expression is induced in the renal interstitium following unilateral ureter obstruction (UUO), where it is expressed by activated fibroblasts. Ybx3-deficient mice show significantly reduced tissue injury, immune cell infiltration, and extracellular matrix deposition compared with wild-type in the UUO model. Ybx3 knockout mouse UUO model; RNAseq; immunohistochemistry for fibrosis and immune markers; extracellular matrix analysis Cells Medium 37408260
2024 YBX3 is an RNA-binding protein critical for brown adipocyte differentiation and thermogenesis. YBX3 stabilizes the mRNAs of Slc3a2 and Pparg, facilitating BCAA influx and catabolism as fuel for thermogenesis. BAT-specific loss of Ybx3 in mice dampens thermogenesis and exacerbates diet-induced obesity; overexpression promotes thermogenesis and protects against metabolic dysfunction. In vitro loss- and gain-of-function in C3H10T1/2 preadipocytes and brown adipocytes; AAV-mediated BAT-specific Ybx3 KD/OE in mice; transcriptome analysis; mRNA stability assays; mitochondrial stress test; BCAA/metabolite analysis Molecular metabolism High 39481849
2025 USP5 promotes lysosomal degradation of YBX3 in colorectal cancer, which stabilizes SLC7A11 and suppresses ferroptosis. Under normal conditions, YBX3 promotes SLC7A11 degradation; USP5-mediated YBX3 degradation relieves this, allowing SLC7A11 stabilization and cancer cell survival. YBX3 knockout restored SLC7A11 stability in USP5-deficient cells. USP5 and YBX3 knockout in CRC cells; patient-derived organoid and xenograft models; lysosomal degradation assays; SLC7A11 stability analysis; ferroptosis assays Cell death & disease Medium 41213937
2025 CHK2, YBX1, and YBX3 form a protein complex (identified by IP-MS and phosphoproteomics) that represses pro-inflammatory gene transcription in glioma cells. These proteins positively regulate each other's expression. ChIP-seq revealed common inflammatory genes repressed by the CHK2-YBX1&YBX3 hub. Targeting YBX1 with inhibitor SU056 degrades the entire hub, leading to enhanced antigen presentation and CD8+ T cell activation. Immunoprecipitation + mass spectrometry + phosphoproteomics; single-gene KO of CHEK2, YBX1, YBX3; RNA-seq; ChIP-seq; YBX1 inhibitor SU056; in vivo glioma survival studies Neuro-oncology / bioRxiv Medium 40161682 41025501

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. The Journal of cell biology 311 12566432
2001 Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proceedings of the National Academy of Sciences of the United States of America 294 11675503
2004 CsdA, a cold-shock RNA helicase from Escherichia coli, is involved in the biogenesis of 50S ribosomal subunit. Nucleic acids research 202 15148362
2006 Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Molecular and cellular biology 181 16508013
2004 Physical and functional interactions among RNase E, polynucleotide phosphorylase and the cold-shock protein, CsdA: evidence for a 'cold shock degradosome'. Molecular microbiology 157 15554978
1993 DbpA: a DEAD box protein specifically activated by 23s rRNA. The EMBO journal 139 8253085
2001 Escherichia coli DbpA is an RNA helicase that requires hairpin 92 of 23S rRNA. The EMBO journal 126 11574482
1998 Active and passive immunity against Borrelia burgdorferi decorin binding protein A (DbpA) protects against infection. Infection and immunity 116 9573101
1991 DNA binding properties of YB-1 and dbpA: binding to double-stranded, single-stranded, and abasic site containing DNAs. Nucleic acids research 113 1923758
2014 CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway. Journal of cell science 108 25107366
2007 The ATPase cycle mechanism of the DEAD-box rRNA helicase, DbpA. Journal of molecular biology 102 18237742
2010 The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PloS one 101 21209887
2005 Analysis of the heteromeric CsdA-CsdE cysteine desulfurase, assisting Fe-S cluster biogenesis in Escherichia coli. The Journal of biological chemistry 95 15901727
2010 ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. Journal of the American Society of Nephrology : JASN 94 20133480
2005 Expression of zonula occludens-1 (ZO-1) and the transcription factor ZO-1-associated nucleic acid-binding protein (ZONAB)-MsY3 in glial cells and colocalization at oligodendrocyte and astrocyte gap junctions in mouse brain. The European journal of neuroscience 89 16045494
2001 The Escherichia coli DEAD protein DbpA recognizes a small RNA hairpin in 23S rRNA. RNA (New York, N.Y.) 87 11350034
2000 Decorin-binding protein A (DbpA) of Borrelia burgdorferi is not protective when immunized mice are challenged via tick infestation and correlates with the lack of DbpA expression by B. burgdorferi in ticks. Infection and immunity 87 10899883
2002 Effects of ribosomal proteins S1, S2 and the DeaD/CsdA DEAD-box helicase on translation of leaderless and canonical mRNAs in Escherichia coli. Molecular microbiology 86 12068815
2004 RalA interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity. The EMBO journal 85 15592429
2010 Pathway of ATP utilization and duplex rRNA unwinding by the DEAD-box helicase, DbpA. Proceedings of the National Academy of Sciences of the United States of America 77 20160110
1998 Kinetic analysis of the RNA-dependent adenosinetriphosphatase activity of DbpA, an Escherichia coli DEAD protein specific for 23S ribosomal RNA. Biochemistry 72 9836593
1995 The "DEAD box" protein DbpA interacts specifically with the peptidyltransferase center in 23S rRNA. Proceedings of the National Academy of Sciences of the United States of America 72 8524828
1997 Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins. Molecular and cellular biology 63 8972186
2002 Cooperative binding of ATP and RNA substrates to the DEAD/H protein DbpA. Biochemistry 62 11888286
2019 The RNA-Binding Protein YBX3 Controls Amino Acid Levels by Regulating SLC mRNA Abundance. Cell reports 61 31189097
2009 A dominant negative mutant of the E. coli RNA helicase DbpA blocks assembly of the 50S ribosomal subunit. Nucleic acids research 61 19734347
2007 Complementation analysis of the cold-sensitive phenotype of the Escherichia coli csdA deletion strain. Journal of bacteriology 60 17557820
2006 Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. Journal of cell science 57 17158914
2011 Allelic variation of the Lyme disease spirochete adhesin DbpA influences spirochetal binding to decorin, dermatan sulfate, and mammalian cells. Infection and immunity 54 21708995
2008 Ribosome assembly in Escherichia coli strains lacking the RNA helicase DeaD/CsdA or DbpA. The FEBS journal 54 18565105
2003 Significant improvement of the recombinant Borrelia-specific immunoglobulin G immunoblot test by addition of VlsE and a DbpA homologue derived from Borrelia garinii for diagnosis of early neuroborreliosis. Journal of clinical microbiology 54 12624072
2009 The CsdA cysteine desulphurase promotes Fe/S biogenesis by recruiting Suf components and participates to a new sulphur transfer pathway by recruiting CsdL (ex-YgdL), a ubiquitin-modifying-like protein. Molecular microbiology 52 20054882
2006 The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB. Molecular biology of the cell 51 16407410
1995 Characterization of the gene for dbpA, a family member of the nucleic-acid-binding proteins containing a cold-shock domain. European journal of biochemistry 51 7628487
2001 Visualization of unwinding activity of duplex RNA by DbpA, a DEAD box helicase, at single-molecule resolution by atomic force microscopy. Proceedings of the National Academy of Sciences of the United States of America 48 11296244
2018 Hypoxia-induced microRNA-191 contributes to hepatic ischemia/reperfusion injury through the ZONAB/Cyclin D1 axis. Cell death and differentiation 47 29769640
2009 The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription. EMBO reports 46 19730435
2008 Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions. The European journal of neuroscience 46 18973575
1999 Interaction of the Escherichia coli DEAD box protein DbpA with 23 S ribosomal RNA. Journal of molecular biology 44 10525403
2007 Mutation of the arginine finger in the active site of Escherichia coli DbpA abolishes ATPase and helicase activity and confers a dominant slow growth phenotype. Nucleic acids research 42 17986459
2005 Equilibrium and kinetic analysis of nucleotide binding to the DEAD-box RNA helicase DbpA. Biochemistry 40 15654752
1997 Positive and negative regulation of the human thymidine kinase promoter mediated by CCAAT binding transcription factors NF-Y/CBF, dbpA, and CDP/cut. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 40 9419421
2023 M6A-mediated-upregulation of lncRNA BLACAT3 promotes bladder cancer angiogenesis and hematogenous metastasis through YBX3 nuclear shuttling and enhancing NCF2 transcription. Oncogene 39 37612524
2013 Structural changes during cysteine desulfurase CsdA and sulfur acceptor CsdE interactions provide insight into the trans-persulfuration. The Journal of biological chemistry 38 23913692
2004 Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis. Biochemical and biophysical research communications 37 15313206
2003 Diagnosis of Lyme neuroborreliosis with antibodies to recombinant proteins DbpA, BBK32, and OspC, and VlsE IR6 peptide. Journal of neurology 37 14648148
2007 Mutational analysis of the Escherichia coli DEAD box protein CsdA. Journal of bacteriology 36 17259309
2006 Molecular analysis of decorin-binding protein A (DbpA) reveals five major groups among European Borrelia burgdorferi sensu lato strains with impact for the development of serological assays and indicates lateral gene transfer of the dbpA gene. International journal of medical microbiology : IJMM 36 16530482
2009 The symplekin/ZONAB complex inhibits intestinal cell differentiation by the repression of AML1/Runx1. Gastroenterology 34 19328795
2014 ZO proteins redundantly regulate the transcription factor DbpA/ZONAB. The Journal of biological chemistry 33 24986862
2010 Requirement of the CsdA DEAD-box helicase for low temperature riboregulation of rpoS mRNA. RNA biology 32 21045550
2007 Phosphatidylethanol accumulation promotes intestinal hyperplasia by inducing ZONAB-mediated cell density increase in response to chronic ethanol exposure. Molecular cancer research : MCR 31 18025260
2004 Interaction of Escherichia coli DbpA with 23S rRNA in different functional states of the enzyme. Nucleic acids research 31 15173385
2005 Escherichia coli DbpA is a 3' --> 5' RNA helicase. Biochemistry 28 15910005
2014 Identification of lysine residues in the Borrelia burgdorferi DbpA adhesin required for murine infection. Infection and immunity 27 24842928
1997 Characterization of DbpA, an Escherichia coli DEAD box protein with ATP independent RNA unwinding activity. Nucleic acids research 27 9016593
2021 YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling. Frontiers in oncology 25 33816248
2021 Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3. Chinese medical journal 24 33480613
2015 Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin. Biochemical and biophysical research communications 24 26106824
2012 Escherichia coli cold-shock gene profiles in response to over-expression/deletion of CsdA, RNase R and PNPase and relevance to low-temperature RNA metabolism. Genes to cells : devoted to molecular & cellular mechanisms 23 22957931
2017 Insights into the Structure of Dimeric RNA Helicase CsdA and Indispensable Role of Its C-Terminal Regions. Structure (London, England : 1993) 22 29107486
2002 Somatic mutation and SNP in the promoter of dbpA and human hepatocarcinogenesis. International journal of oncology 22 12239625
2021 Structural basis for the activation of the DEAD-box RNA helicase DbpA by the nascent ribosome. Proceedings of the National Academy of Sciences of the United States of America 21 34453003
2002 The RNA helicase DbpA exhibits a markedly different conformation in the ADP-bound state when compared with the ATP- or RNA-bound states. The Journal of biological chemistry 21 12324462
2009 Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells. Acta pharmacologica Sinica 20 19749785
1999 DNA binding protein dbpA binds Cdk5 and inhibits its activity. FEBS letters 19 10100871
2022 Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer. Frontiers in immunology 18 36059530
2016 Time course of large ribosomal subunit assembly in E. coli cells overexpressing a helicase inactive DbpA protein. RNA (New York, N.Y.) 18 27194011
2005 Hydrodynamic characterization of the DEAD-box RNA helicase DbpA. Journal of molecular biology 18 16325852
2011 Requirement for RNA helicase CsdA for growth of Yersinia pseudotuberculosis IP32953 at low temperatures. Applied and environmental microbiology 17 22156424
2023 Silencing circSERPINE2 restrains mesenchymal stem cell senescence via the YBX3/PCNA/p21 axis. Cellular and molecular life sciences : CMLS 15 37831180
2017 DbpA is a region-specific RNA helicase. Biopolymers 15 27813083
2011 Probing conformational variations at the ATPase site of the RNA helicase DbpA by high-field electron-nuclear double resonance spectroscopy. Journal of the American Chemical Society 15 21819147
2010 Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma. Clinical & experimental metastasis 15 20623179
2013 Characterization of the kinetics of RNA annealing and strand displacement activities of the E. coli DEAD-box helicase CsdA. RNA biology 12 23291905
2023 Structural basis for RNA-duplex unwinding by the DEAD-box helicase DbpA. RNA (New York, N.Y.) 11 37221012
2023 Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex. Nature communications 10 37963872
2016 The DbpA catalytic core unwinds double-helix substrates by directly loading on them. RNA (New York, N.Y.) 10 26755693
2023 The YBX3 RNA-binding protein posttranscriptionally controls SLC1A5 mRNA in proliferating and differentiating skeletal muscle cells. The Journal of biological chemistry 9 38159852
2019 Modulation of Contact Inhibition by ZO-1/ZONAB Gene Transfer-A New Strategy to Increase the Endothelial Cell Density of Corneal Grafts. Investigative ophthalmology & visual science 9 31335954
2017 Kinetics and Thermodynamics of DbpA Protein's C-Terminal Domain Interaction with RNA. ACS omega 9 29214235
2011 Escherichia coli cold shock protein CsdA effects an increase in septation and the resultant formation of coccobacilli at low temperature. Archives of microbiology 9 21359956
2005 MZF-1 and DbpA interact with DNase I hypersensitive sites that correlate with expression of the human MUC1 mucin gene. Experimental cell research 9 15893750
2022 RNA Post-Transcriptional Modifications in Two Large Subunit Intermediates Populated in E. coli Cells Expressing Helicase Inactive R331A DbpA. Biochemistry 8 35481783
2020 Y-Box-Binding Protein 3 (YBX3) Restricts Influenza A Virus by Interacting with Viral Ribonucleoprotein Complex and Imparing its Function. The Journal of general virology 8 32553055
2018 Decreased ZONAB expression promotes excessive transdifferentiation of alveolar epithelial cells in hyperoxia-induced bronchopulmonary dysplasia. International journal of molecular medicine 7 29393348
2024 RNA-binding protein YBX3 promotes PPARγ-SLC3A2 mediated BCAA metabolism fueling brown adipogenesis and thermogenesis. Molecular metabolism 6 39481849
2020 DNA sequence-specific ligands. XVIII. Synthesis, physico-chemical properties; genetic, virological, and biochemical studies of fluorescent dimeric bisbenzimidazoles DBPA(n). Bioorganic & medicinal chemistry 5 32089391
2015 Functional csdA is needed for effective adaptation and initiation of growth of Clostridium botulinum ATCC 3502 at suboptimal temperature. International journal of food microbiology 5 26057109
2012 Cold-shock-domain protein A (CSDA) contributes posttranscriptionally to gonadotropin-releasing hormone-regulated expression of Egr1 and indirectly to Lhb. Biology of reproduction 5 22053098
2018 Bradykinin potentially stimulates cell proliferation in rabbit corneal endothelial cells through the ZO‑1/ZONAB pathway. International journal of molecular medicine 4 29568941
2013 Stopping power and CSDA range calculations for incident electrons and positrons in breast and brain tissues. Radiation and environmental biophysics 4 23334249
2026 YBX1&YBX3 as novel targets to potentiate immune checkpoint blockade response in gliomas. Neuro-oncology 3 41025501
2025 USP5 regulates ferroptosis in colorectal cancer by targeting the YBX3/SLC7A11 axis through lysosomal degradation. Cell death & disease 3 41213937
2023 Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease. Cells 3 37408260
2023 Identification of RNA-binding protein YBX3 as an oncogene in clear cell renal cell carcinoma. Functional & integrative genomics 3 37418046
2022 A novel 27-bp indel in the intron region of the YBX3 gene is associated with growth traits in chickens. British poultry science 3 35382648
2012 Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic syndrome. Hepatology international 3 26201636
2025 Targeting CHEK2-YBX1&YBX3 regulatory hub to potentiate immune checkpoint blockade response in gliomas. bioRxiv : the preprint server for biology 2 40161682
2023 Interplay between bacterial 5'-NAD-RNA decapping hydrolase NudC and DEAD-box RNA helicase CsdA in stress responses. mSystems 2 37706681

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