Affinage

YBX1

Y-box-binding protein 1 · UniProt P67809

Length
324 aa
Mass
35.9 kDa
Annotated
2026-06-11
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YBX1 is a multifunctional cold-shock-domain protein that governs gene expression at both the RNA and DNA levels, operating as a global translational regulator, a sequence-specific transcription factor, and a stress-response coordinator (PMID:11574481, PMID:31944153, PMID:32710623). In the cytoplasm it binds mRNA at or near the cap, stabilizing transcripts and displacing eIF4E (PMID:11574481), and acts as a broad translational repressor whose loss is compensated by upregulation of the paralog YB-3 (PMID:31944153); it forms cooperative homo-multimers on selected mRNAs and DNA structures to confer target selectivity (PMID:26271991). At specific 5'UTRs it switches to translational activation, driving production of G3BP1, NFE2L2, HIF1A, and CCT4, the last of which feeds back to sustain mTOR signaling alongside YBX1 autoregulation (PMID:25800057, PMID:31668005, PMID:35239512). Through G3BP1 control and ATP-independent unwinding of mRNA secondary structure via its cold-shock and disordered C-terminal domains, YBX1 modulates stress granule assembly and disassembly (PMID:25800057, PMID:34469566), and it phase-separates into condensates that sort miR-223 into exosomes (PMID:34766549). In the nucleus YBX1 binds promoter elements to either repress (class II MHC Y-box, AP-1, p16/CDKN2A, grp78, p53 apoptotic targets, HIF-1α-driven EPO) or activate (CCL5, MACC1, BRCA1) transcription depending on cofactors and modification state (PMID:8163940, PMID:15702969, PMID:24165022, PMID:8972186, PMID:16158057, PMID:27524241, PMID:24947514, PMID:28624808, PMID:37489617). Its CSD plus C-terminal extension forms a rigid module that recognizes a broad set of DNA sequences, and phosphorylation at S102 destabilizes the fold and reduces ssDNA binding (PMID:32710623). Nucleocytoplasmic partitioning is the master control point: nuclear import proceeds through transportin-1 recognition of an NLS (PMID:27794479), and is gated by phosphorylation (S102 promotes import; calcineurin dephosphorylation and S209 phosphorylation oppose it), SUMOylation, cell-cycle stage, and partner interactions with HSP60 and FBL (PMID:24947514, PMID:35008856, PMID:32013098, PMID:28008157, PMID:19470374, PMID:37489617). YBX1 stability and secretion are set by ubiquitination, with HACE1-mediated K27-linked chains routing it through TSG101 for extracellular release and PRP19-mediated chains targeting it for degradation (PMID:26343856, PMID:33361760). Additional activities include mitochondrial mismatch repair (PMID:19272840), stimulation of PARP1 and assistance of XPC-HR23B in DNA repair (PMID:29805738, PMID:25756536), JAK2-dependent splicing control in myeloproliferative neoplasms (PMID:33239784), PRC2-coupled regulation of H3K27me3 (PMID:32792512), and roles in cytokinesis, microtubule-dependent MT1-MMP trafficking, NF-κB signaling, and as an extracellular Notch-3 ligand (PMID:32882852, PMID:20599698, PMID:32764479, PMID:19640841).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established that YBX1 is a sequence-specific transcriptional repressor, binding the inverted CCAAT (Y) element to silence inducible immune genes.

    Evidence Co-transfection of YB-1 with promoter-reporter constructs and endogenous MHC II gene readout

    PMID:8163940

    Open questions at the time
    • Did not identify the modifications or cofactors that gate this repression
    • No structural basis for Y-element recognition
  2. 2001 High

    Defined the dual cytoplasmic function of YBX1 as a cap-dependent mRNA stabilizer and an activation-by-cleavage transcription factor, linking mRNA release to nuclear translocation.

    Evidence In vitro mRNA stability and cap-competition assays; biochemical fractionation and thrombin-induced proteolysis with reporter assays

    PMID:11390977 PMID:11574481

    Open questions at the time
    • Physiological protease and trigger for cleavage in non-thrombin contexts unresolved
    • Relationship between cap binding and eIF4E displacement at endogenous loci not mapped
  3. 2002 High

    Showed YBX1 recognizes oxidatively damaged RNA, implicating it in RNA quality control under oxidative stress.

    Evidence In vitro binding to 8-oxoguanine RNA with deletion mutants and bacterial oxidative-stress resistance assay

    PMID:12379116

    Open questions at the time
    • Fate of bound oxidized RNA in mammalian cells unknown
    • Whether this binding alters translation of damaged transcripts untested
  4. 2009 Medium

    Extended YBX1 function beyond the nucleus/cytoplasm to mitochondrial mismatch repair and to extracellular Notch-3 ligand activity, revealing a remarkably broad localization repertoire.

    Evidence Mitochondrial fractionation with MMR assays and mtDNA mutagenesis quantification; co-IP and Notch reporter assays distinguishing Notch-3 from Notch-1

    PMID:19272840 PMID:19640841

    Open questions at the time
    • Mitochondrial import mechanism and partner repair factors unidentified
    • Notch-3 ligand role rests on a single lab without independent confirmation
  5. 2015 High

    Resolved how YBX1 achieves mRNA-target selectivity and how it controls stress granule biogenesis, linking translational control to RNA homeostasis.

    Evidence Cooperative multimerization and translation reporter assays; 5'UTR binding/translational activation of G3BP1; tRF-mediated displacement of 3'UTRs from YBX1 (RIP, LNA, synthetic mimetics)

    PMID:25800057 PMID:25957686 PMID:26271991

    Open questions at the time
    • Structural basis distinguishing multimerizing from non-multimerizing targets unclear
    • How tRF abundance is set physiologically not addressed
  6. 2016 High

    Identified transportin-1 as the import receptor and converging phosphorylation/SUMOylation inputs as the switch controlling YBX1 nuclear access and compartment-specific transcriptional outputs.

    Evidence In vitro nuclear import assays with NLS mutagenesis and M9M inhibition; S102/calcineurin co-IP and ChIP; HIF-1α co-IP and HRE binding; circadian SUMOylation with cyclin A2 ChIP in zebrafish

    PMID:24947514 PMID:27524241 PMID:27794479 PMID:28008157

    Open questions at the time
    • Integration of competing phospho/SUMO signals into a single localization decision not unified
    • Stimulus specificity of each input incompletely mapped
  7. 2016 High

    Demonstrated compartment-segregated, opposing functions of YBX1 on the same target gene (cytoplasmic mRNA stabilization vs nuclear promoter repression), providing a clean in vivo model of localization-dependent activity.

    Evidence mRNA stability assays, half-knockout mice, and small-molecule nuclear shuttling in a renal fibrosis model

    PMID:27591085

    Open questions at the time
    • Whether this compartmental antagonism generalizes beyond Col1a1 untested
  8. 2018 Medium

    Connected YBX1 to DNA repair pathways as a PARP1 cofactor and an XPC-HR23B partner, broadening its DNA-associated roles beyond transcription.

    Evidence In vitro PARP1 activity assays with domain deletions; NER substrate binding/stimulation assays with purified proteins

    PMID:25756536 PMID:29805738

    Open questions at the time
    • In vitro reconstitution awaits cellular validation of repair contribution
    • C-terminal domain mechanism of PARP1 stimulation not structurally defined
  9. 2019 High

    Pinpointed K81 acetylation as a regulatory switch that disables 5'UTR binding and translational activation of oncogenic targets, defining a druggable post-translational control point.

    Evidence Acetylomics, MS-275 treatment, K81A rescue mutant, mRNA binding and in vivo metastasis assays

    PMID:31668005

    Open questions at the time
    • Acetyltransferase responsible for K81 not identified
    • Interplay between acetylation and phosphorylation at adjacent sites unresolved
  10. 2020 High

    Provided the structural and mechanistic foundation for YBX1 as a global translation repressor, an ATP-independent RNA chaperone, a PRC2-coupled chromatin regulator, and a JAK2-dependent splicing factor, with the CSDex defining its DNA-binding breadth.

    Evidence Crystal/NMR structure with phosphomimetic DNA-binding assays; Ribo-Seq/RIP-Seq in knockouts; in vitro unwinding with domain mutants; Co-IP/ChIP-seq with PRC2; phosphoproteomics and RNA-seq in JAK2V617F models

    PMID:31944153 PMID:32710623 PMID:32792512 PMID:33239784 PMID:34469566

    Open questions at the time
    • How a single protein partitions between repression, unwinding, splicing, and chromatin roles in one cell is unresolved
    • Direct structural model of YBX1-PRC2 contact lacking
  11. 2020 Medium

    Established phase separation as the mechanism for selective miR-223 sorting into exosomes and refined the multi-site phospho-code controlling cell-cycle-timed nuclear entry and cytokinesis.

    Evidence In vitro LLPS with phase-separation mutants and exosome miRNA quantification; live-cell imaging with MS phosphosite mapping and MD simulations across cell-cycle and cytokinesis studies

    PMID:32013098 PMID:32882852 PMID:34766549

    Open questions at the time
    • Determinants of selective miRNA recruitment into condensates incompletely defined
    • Kinases for individual cell-cycle phosphosites not all assigned
  12. 2020 Medium

    Mapped ubiquitin-dependent control of YBX1 fate, with K27-linked chains (HACE1) driving secretion via TSG101 and PRP19-mediated chains driving degradation, the latter blockable by a stabilizing circRNA.

    Evidence Ubiquitination/co-IP and secretion assays for HACE1-K27-TSG101; RNA pulldown/co-IP and ubiquitination readout for circRNA-SORE/PRP19

    PMID:26343856 PMID:33361760

    Open questions at the time
    • Signals selecting between secretory and degradative ubiquitination unknown
    • Both findings rest on single labs
  13. 2021 Medium

    Showed YBX1 directly promotes polysomal translation of MYC and other oncogenic drivers, tying its translational activity to malignant fitness.

    Evidence Polysome fractionation with CRISPR inactivation and competitive in vivo assays

    PMID:34465866

    Open questions at the time
    • Distinction from global repressor role on the same transcripts not mechanistically reconciled
    • Recruitment determinants to polysomes undefined
  14. 2024 Medium

    Connected YBX1 to endothelial stress-granule biology through ZO-1 sequestration, defining a stress-released pool that drives cytoprotective granule formation in vivo.

    Evidence Co-IP, arsenite stress granule assays, and endothelial ZO-1 knockout mice with retinal vasculature imaging

    PMID:38782923

    Open questions at the time
    • Reciprocal regulation of ZO-1 by YBX1 not established
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How YBX1's many activities are coordinated within a single cell—which modifications, partners, and condensate states select among translation repression/activation, transcription, splicing, repair, and secretion—remains unresolved.
  • No unified model linking post-translational code to functional state selection
  • Quantitative partitioning of YBX1 pools across compartments and condensates unmeasured
  • Endogenous physiological triggers for many in vitro activities undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 9 GO:0003723 RNA binding 9 GO:0045182 translation regulator activity 6 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 11 GO:0000228 nuclear chromosome 6 GO:0005829 cytosol 5 GO:0005856 cytoskeleton 3 GO:0005576 extracellular region 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-162582 Signal Transduction 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-73894 DNA Repair 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 1

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 YB-1 (p50) is a potent cap-dependent mRNA stabilizer; its cold shock domain mediates mRNA stabilizing activity, and YB-1 destabilizes the interaction of eIF4E with the mRNA cap structure while itself associating with mRNA at or near the cap when eIF4E is sequestered. In vitro mRNA stability assays, in vivo overexpression/depletion, cap-binding competition assays The EMBO journal High 11574481
2001 YB-1 (dbpB) is activated by proteolytic cleavage upon thrombin stimulation, which releases it from mRNA in the cytoplasm, allowing nuclear translocation and transcriptional activation of target genes including PDGF-B; cytosolic retention is mediated by region 247–267 which is cleaved during activation. Biochemical fractionation, oligo(dT) affinity chromatography, immunoprecipitation, RNase treatment, reporter gene assays, nuclear localization imaging Proceedings of the National Academy of Sciences of the United States of America High 11390977
2002 YB-1 binds specifically to RNA containing 8-oxoguanine (oxidized RNA) but not normal RNA; domain deletion mapping identified the regions required for this binding; expression of YB-1 in E. coli confers resistance to oxidative stress in a binding-activity-dependent manner. In vitro RNA-binding assays with purified protein, deletion mutant analysis, bacterial oxidative-stress resistance assay Biochemistry High 12379116
1994 YB-1 represses IFN-γ-induced transcription of class II MHC genes (HLA-DR) and the Invariant chain gene by binding the Y element (inverted CCAAT box) in their promoters. Co-transfection of YB-1 expression vector with promoter-reporter constructs, transient transfection with >70% efficiency, mRNA and antigen expression analysis The Journal of experimental medicine High 8163940
2009 YB-1 localizes to human mitochondria, contributes to mitochondrial mismatch-binding and mismatch-repair activity, and its depletion increases mitochondrial DNA mutagenesis; mitochondrial MMR is distinct from nuclear MMR and does not require canonical nuclear MMR factors such as MSH2. Subcellular fractionation, mitochondrial extract MMR assays, siRNA depletion, mitochondrial DNA mutagenesis quantification DNA repair High 19272840
2009 Extracellular secreted YB-1 acts as a ligand for Notch-3 receptor (but not Notch-1), interacting with its extracellular domain; this interaction activates Notch-3 signaling, leading to nuclear translocation of the Notch-3 intracellular domain and upregulation of Notch target genes. Co-immunoprecipitation, co-localization at cell membranes (GFP fusion), reporter assays for Notch target genes, binding specificity assays comparing Notch-1 vs Notch-3 The Journal of biological chemistry Medium 19640841
2009 HSP60 binds to YB-1 at the YB-NLS region in the cytoplasm, and this interaction regulates YB-1 polysome association and subcellular distribution; HSP60 overexpression decreases YB-1 in heavy-sedimenting polysome fractions and suppresses YB-NLS-mediated nuclear import. Co-immunoprecipitation, sucrose gradient sedimentation, overexpression/knockdown of HSP60, nuclear localization assays Biochemical and biophysical research communications Medium 19470374
2008 YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro; high-resolution microscopy shows YB-1 coats the outer microtubule wall; tubulin binding interferes with RNA:YB-1 complexes. In vitro microtubule assembly assays, electron microscopy, atomic force microscopy, co-sedimentation assays, RNA competition assays BMC biochemistry Medium 18793384
2015 tRNA-derived fragments (tRFs) from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) suppress the stability of oncogenic transcripts by displacing their 3'UTRs from YBX1; these tRFs share a common motif matching the YBX1 recognition sequence, demonstrating sequence-specific displacement of mRNAs from YBX1. RNA-binding protein immunoprecipitation, LNA loss-of-function, synthetic RNA mimetics gain-of-function, in vitro displacement assays, invasion/metastasis assays Cell High 25957686
2015 YB-1 directly binds to and translationally activates the 5'UTR of G3BP1 mRNA, controlling G3BP1 protein availability for stress granule (SG) nucleation; YB-1 inactivation dramatically reduces G3BP1 protein and SG formation. Direct RNA binding assays (5'UTR), translational reporter assays, YB-1 siRNA knockdown, in vivo xenograft SG formation analysis The Journal of cell biology High 25800057
2015 HACE1 E3 ubiquitin ligase polyubiquitinates YB-1 via non-canonical K27-linked ubiquitin chains; this ubiquitination promotes YB-1 interaction with TSG101 (a component of the MVB pathway) and is required for YB-1 extracellular secretion. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, secretion assays Cellular signalling Medium 26343856
2016 Transportin-1 mediates YB-1 nuclear import; YB-1 and transportin-1 form a complex in HeLa cell extracts; nuclear import is abolished by a transportin-1 competitor substrate, the transportin-1 inhibitor M9M, and inactivating mutations in the transportin-1-dependent NLS (P201A/Y202A). In vitro nuclear import assay, co-immunoprecipitation from cell extracts, site-directed mutagenesis of NLS, pharmacological inhibition Biochemical and biophysical research communications High 27794479
2016 YB-1 phosphorylation at serine 102 promotes its nuclear translocation and CCL5 promoter binding; calcineurin (CN) dephosphorylates YB-1 at S102, reducing its CCL5 transcriptional activation; YB-1/CN interact directly by co-immunoprecipitation. Co-immunoprecipitation, ChIP, reporter assays, calcineurin inhibitor (cyclosporine A) treatment in vivo and in vitro, phospho-specific antibodies The Journal of biological chemistry High 24947514
2019 Class I HDAC inhibitor MS-275 promotes YB-1 acetylation at lysine-81, blocking its binding to 5'UTRs of NFE2L2 (NRF2), HIF1A, and G3BP1 mRNAs and thereby reducing their translation; an MS-275-resistant YB-1(K81A) mutant restores translational activation of these targets and metastatic capacity. Global acetylomics, in vivo metastasis assays, MS-275-resistant point mutant (K81A), mRNA binding assays EMBO reports High 31668005
2020 YB-1 CSD with C-terminal extension (CSDex) adopts a rigid structure (not disordered); phosphorylation of S102 destabilizes the protein and causes partial unfolding; CSDex provides a unique DNA binding site recognizing a broader set of sequences than the canonical CSD; S102 phosphorylation dramatically reduces ssDNA binding. Crystal structure determination, NMR structural characterization, DNA binding assays with phosphomimetic and deletion mutants Nucleic acids research High 32710623
2020 JAK2V617F phosphorylates YB-1 post-translationally; YBX1 inactivation in JAK2-mutated cells causes RNA mis-splicing, intron retention, and disruption of ERK signaling control; YBX1 functions as a splicing factor maintaining disease persistence in myeloproliferative neoplasms. In-depth phosphoproteome profiling, genetic inactivation (CRISPR/shRNA), in vivo mouse and primary human cell models, RNA-seq (splicing analysis) Nature High 33239784
2020 YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells; YBX1 condensates selectively recruit miR-223 in vitro and sort it into exosomes; point mutations inhibiting LLPS impair YBX1 incorporation into biomolecular condensates and perturb miR-223 sorting into exosomes. LLPS in vitro assays, live-cell imaging of condensates, point mutagenesis of phase-separation residues, exosome miRNA quantification eLife High 34766549
2020 YB-1 is a global translation inhibitor that binds a wide range of mRNAs; YBX1 knockout leads to compensatory upregulation of YB-3 translation, which binds a strikingly similar set of mRNAs and substitutes for YB-1 in global translational repression. Ribo-Seq, RIP-Seq, YBX1 knockout cell lines RNA biology High 31944153
2020 Ybx1 interacts with PRC2, highly overlaps PRC2 binding genome-wide, controls PRC2 distribution, and inhibits H3K27me3 levels in neural progenitor cells; Ybx1 knockout increases H3K27me3 and PRC2 enzymatic inhibition partially rescues gene expression and NPC functions. Co-immunoprecipitation (Ybx1-PRC2), ChIP-seq, Ybx1 knockout mice and NPCs, PRC2 inhibitor rescue experiments Nature communications High 32792512
2020 YB-1 dephosphorylation at serine residues 102, 165, and 176 increases accessibility of the nuclear localization signal (NLS) by altering protein conformation, facilitating nuclear entry during late G2/M phase; live-cell imaging shows YB-1 is primarily perinuclear during G1/S and enters the nucleus at late G2/M. Confocal microscopy, live-cell imaging, mass spectrometry (phosphorylation mapping), atomistic molecular dynamics simulations Cancers Medium 32013098
2019 Inhibition of RNA polymerase II activity results in nuclear accumulation of YB-1 accompanied by its phosphorylation at Ser102; kinase inhibition reduces YB-1 phosphorylation and nuclear accumulation; nuclear RNA is required for nuclear retention of YB-1. RNAPII inhibitor treatment, kinase inhibitors, subcellular fractionation, immunofluorescence, RNA depletion experiments Cells Medium 31906126
2021 YB-1 phosphorylation at Ser209 (by Akt kinase in vitro) inhibits YB-1 nuclear translocation and prevents S102-phosphorylation-mediated nuclear import; phosphomimetic S209E substitution blocks nuclear entry. In vitro Akt kinase assay, phosphomimetic substitutions (S209E), subcellular localization assays International journal of molecular sciences Medium 35008856
2021 YB-1 unwinds mRNA secondary structures without ATP consumption using its cold shock domain to destabilize RNA stem/loops and its unstructured C-terminal domain to secure RNA unwinding; at endogenous levels YB-1 facilitates stress granule disassembly, and overexpression inhibits SG assembly. In vitro RNA unwinding assays, unwinding-defective mutants, arsenite stress granule assays in HeLa cells, live-cell imaging Nucleic acids research High 34469566
2021 YBX1 promotes translation of oncogenic transcripts including MYC by recruitment to polysomal chains; YBX1 genetic inactivation displaces MYC and other oncogenic drivers from polysomes, depleting their protein levels and reducing leukemia cell competitive fitness. Polysome fractionation, genetic inactivation (CRISPR), in vitro and in vivo competitive assays Leukemia Medium 34465866
2018 YB-1 acts as a potent cofactor of PARP1, stimulating its poly(ADP-ribose) polymerase activity; the C-terminal domain of YB-1 is indispensable for PARP1 stimulation; functional interactions between YB-1 and PARP1 can be mediated by poly(ADP-ribose). In vitro PARP1 activity assays with purified YB-1, domain deletion analysis, PAR binding assays Oncotarget Medium 29805738
2015 YB-1 forms stable homo-multimers cooperatively on specific mRNAs (but not others), enabling selective translational inhibition of mRNAs on which stable multimers form; the same cooperative multimerization mechanism also operates on specific DNA structures. In vitro binding and multimerization assays, translation reporter assays, DNA binding studies Nucleic acids research Medium 26271991
2012 YB-1 synthesis is regulated by the mTOR signaling pathway; inhibition of mTOR with PP242 (but not rapamycin) specifically suppresses YB-1 translation; this dependence is dictated by the 5'UTR of YB-1 mRNA as shown by reporter constructs. mTOR inhibitor treatment (PP242/rapamycin), reporter constructs with YB-1 5'UTR, Western and Northern blotting PloS one Medium 23285076
2020 CircRNA-SORE binds YBX1 in the cytoplasm, preventing its interaction with E3 ubiquitin ligase PRP19 and thus blocking PRP19-mediated YBX1 degradation; this stabilizes YBX1 and confers sorafenib resistance in hepatocellular carcinoma. RNA pulldown, co-immunoprecipitation, in vitro and in vivo models, siRNA knockdown Signal transduction and targeted therapy Medium 33361760
2022 YB-1 binds the 5'UTR of CCT4 mRNA to promote CCT4 translation; CCT4 (a CCT chaperone component) activates mTOR signaling by promoting mLST8 folding; YB-1 also autoregulates its own translation by binding its 5'UTR, sustaining mTOR activation. RNA immunoprecipitation, 5'UTR reporter assays, genetic knockdown, xenograft model with RNA decoys, co-expression analysis in patient samples The Journal of clinical investigation Medium 35239512
2023 FBL (fibrillarin) interacts with YBX1 and promotes its nuclear accumulation in response to DNA damage; nuclear YBX1 binds the BRCA1 promoter to activate BRCA1 expression, supporting homologous recombination-mediated DNA repair. Co-immunoprecipitation, ChIP assay, knockdown experiments, DNA damage repair assays EMBO reports Medium 37489617
2016 YB-1 binds to HIF-1α by co-immunoprecipitation and to hypoxia-response element (HRE) sequences (single- and double-stranded) by DNA binding assays; under hypoxia, YB-1 translocates to the nucleus and represses HIF-1α-mediated EPO transcription. Co-immunoprecipitation, DNA binding assays, siRNA depletion, reporter assays, immunofluorescence for nuclear shuttling Biochemical and biophysical research communications Medium 27524241
2016 Cytoplasmic YB-1 directly stabilizes Col1a1 mRNA to promote renal fibrosis; conversely, nuclear (S102-phosphorylated) YB-1 represses the Col1a1 promoter; forced nuclear YB-1 shuttling by small molecule HSc025 is anti-fibrotic in vivo. mRNA stability assays, subcellular fractionation, YB-1 half-knockout mouse model, small molecule nuclear shuttling, fibrosis quantification in vivo Kidney international High 27591085
2015 YB-1 promotes microtubule-dependent trafficking and recycling of MT1-MMP to cell surface invasion sites, increasing breast cancer invasion and metastasis. YB-1/EGFP transfection, immunofluorescence localization to invadopodia, MT1-MMP endocytosis/recycling rate measurements, in vivo tumor formation Biochemical and biophysical research communications Medium 20599698
2005 YB-1 represses AP-1-dependent transcription and directly binds to the AP-1 DNA sequence; a 49 kDa YB-1 protein was purified from cancer cells by DNA-affinity chromatography and confirmed by tandem MS and immunoblotting to bind the AP-1 sequence specifically. DNA-affinity chromatography (NAPSTER assay), tandem MS sequencing, gel mobility supershift assays, luciferase reporter transfection assays The Biochemical journal Medium 15702969
2005 YB-1 inhibits p53-dependent apoptotic gene transactivation (e.g., Bax) without affecting p53-mediated activation of CDKN1A or MDM2; nuclear YB-1 selectively alters p53 transcriptional activity; transcriptionally active p53 is required for YB-1 nuclear localization. Co-transfection reporter assays, apoptosis assays, Bax protein quantification, p53-null and p53-expressing cell comparisons Oncogene Medium 16158057
2017 YB-1 directly binds the MACC1 promoter (demonstrated by ChIP) and activates MACC1 transcription, thereby activating the MACC1/c-Met signaling pathway to promote lung adenocarcinoma progression. ChIP assay, promoter reporter assays, siRNA knockdown, xenograft mouse model Oncotarget Medium 28624808
2013 YB-1 directly binds and represses the p16 (CDKN2A/INK4a) promoter as demonstrated by ChIP; YB1 overexpression decreases p16 expression and promotes cell proliferation while preventing cellular senescence. ChIP assay, overexpression in mouse embryonic fibroblasts, senescence-associated β-galactosidase assay Genes to cells : devoted to molecular & cellular mechanisms Medium 24165022
1997 YB-1 and dbpA bind the lower strand of the SICR (stress-inducible change region) within the grp78 core promoter element and repress stress-inducible (ER stress) transcription; YB-1 interacts with YY1 (identified by yeast two-hybrid) and inhibits YY1 binding to the core element. Expression library screening, gel shift assays, co-transfection reporter assays, yeast interaction trap (two-hybrid) Molecular and cellular biology Medium 8972186
2020 YB-1 depletion causes cytokinesis failure and multinucleation; phosphorylation at six serine residues (including novel sites identified by mass spectrometry) is essential for cytokinesis completion; phosphorylated YB-1 orchestrates spatio-temporal distribution of microtubules, β-actin, and the chromosome passenger complex (CPC) to define the cleavage plane. siRNA knockdown in multiple cell lines, rescue experiments, confocal live-cell imaging, mass spectrometry-based phosphorylation site mapping, atomistic modelling Cancers Medium 32882852
2016 YB-1 is SUMOylated in a circadian-clock-controlled manner in zebrafish; circadian changes in YB-1 SUMOylation regulate its periodic nuclear entry; nuclear YB-1 directly binds the cyclin A2 promoter and downregulates cyclin A2 mRNA expression. SUMOylation assays, live zebrafish imaging, ChIP on cyclin A2 promoter, circadian cycle analysis Oncotarget Medium 28008157
2015 YB-1 interacts with YBX1 target DNA/mRNA structures via cooperative homo-multimerization; YB-1 promotes XPC-HR23B binding to DNA containing bulky NER lesions, and YB-1 and XPC-HR23B mutually stimulate each other's binding to damaged DNA substrates. In vitro DNA binding assays with NER substrate mimics, competition/stimulation binding assays with purified proteins Biochemistry. Biokhimiia Medium 25756536
2016 YBX1 and NOD2 directly interact (demonstrated by co-immunoprecipitation and sucrose gradient co-migration); GMDP (muramyl peptide) stimulates formation of higher-molecular-mass YBX1-NOD2 complexes; both YBX1 and NOD2 contribute independently to GMDP-induced NF-κB activation. Co-immunoprecipitation, sucrose gradient centrifugation, NOD2/YBX1 siRNA knockdown, NF-κB reporter assay Innate immunity Medium 27694635
2022 RSK2 phosphorylates YB-1 at Ser102, promoting formation of a YB-1/KLF5 transcriptional complex that co-regulates BLBC-specific genes (KRT16, Ly6D); YB-1 also stabilizes KLF5 mRNA in an RNA 5-methylcytosine modification-dependent manner. Co-immunoprecipitation, ChIP, luciferase reporter assays, RSK inhibitor (LJH685), mRNA stability assays, in vivo xenograft Cell death and differentiation Medium 35022570
2024 ZO-1 physically interacts with YB-1 in endothelial cells; arsenite treatment decreases ZO-1/YB-1 interaction and drives YB-1 into stress granules; YB-1 is essential for stress granule formation and for the cytoprotective effects of ZO-1 downregulation during angiogenesis. Co-immunoprecipitation, arsenite stress granule assays, endothelial-specific ZO-1 knockout mice, confocal imaging of YB-1 granules in retinal vasculature Nature communications Medium 38782923
2020 YB-1 mediates TNF-induced NF-κB activation by maintaining expression of TRAF2, a central component of the TNFR1 signaling complex; YB-1-deficient cells show reduced TRAF2 expression and enhanced apoptosis in response to TNF. YB-1 knockout/knockdown cells, TNF stimulation, NF-κB reporter assays, caspase-3 activation, zVAD rescue Cancers Medium 32764479
2013 YB-1 stabilizes HIV-1 genomic RNA by binding to the stem loop 2 of the HIV-1 RNA packaging signal (mapped as the YB-1-responsive element), thereby enhancing HIV-1 protein expression and viral production. YB-1 overexpression/knockdown in producer cells, viral production quantification, RNA stability assays, deletion mapping of responsive element Protein & cell Medium 23589019

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell 736 25957686
2003 The pleiotropic functions of the Y-box-binding protein, YB-1. BioEssays : news and reviews in molecular, cellular and developmental biology 432 12815724
2020 CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal transduction and targeted therapy 371 33361760
2013 YB-1 protein: functions and regulation. Wiley interdisciplinary reviews. RNA 321 24217978
2011 Y-box-binding protein 1 (YB-1) and its functions. Biochemistry. Biokhimiia 312 22339596
2001 The major mRNA-associated protein YB-1 is a potent 5' cap-dependent mRNA stabilizer. The EMBO journal 239 11574481
2015 YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1. The Journal of cell biology 224 25800057
2021 Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription. Journal of hepatology 185 34509526
2009 Novel DNA mismatch-repair activity involving YB-1 in human mitochondria. DNA repair 162 19272840
2004 YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. The Prostate 149 15042610
2008 Twist promotes tumor cell growth through YB-1 expression. Cancer research 135 18172301
2021 Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates. eLife 134 34766549
2020 Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms. Nature 131 33239784
1999 Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas. International journal of cancer 122 10597187
2013 Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y? Cell death and differentiation 104 23449390
2002 Binding capacity of human YB-1 protein for RNA containing 8-oxoguanine. Biochemistry 102 12379116
2011 YB-1, the E2F pathway, and regulation of tumor cell growth. Journal of the National Cancer Institute 96 22205655
2003 The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies. Cancer science 95 12708467
2019 Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis. EMBO reports 94 31668005
2021 A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance. Cellular signalling 88 34224843
2009 YB-1 acts as a ligand for Notch-3 receptors and modulates receptor activation. The Journal of biological chemistry 85 19640841
2005 Y-box factor YB1 controls p53 apoptotic function. Oncogene 84 16158057
1994 YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. The Journal of experimental medicine 83 8163940
2018 YBX1 at the crossroads of non-coding transcriptome, exosomal, and cytoplasmic granular signaling. European journal of cell biology 75 29478751
2022 YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer. Cell death and differentiation 65 35022570
2015 YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment. Oncotarget 64 25980435
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
2019 Hypoxia-induced H19/YB-1 cascade modulates cardiac remodeling after infarction. Theranostics 62 31588235
2022 Upregulated YB-1 protein promotes glioblastoma growth through a YB-1/CCT4/mLST8/mTOR pathway. The Journal of clinical investigation 58 35239512
2015 HACE1 mediated K27 ubiquitin linkage leads to YB-1 protein secretion. Cellular signalling 55 26343856
2013 YB-1 is an early and central mediator of bacterial and sterile inflammation in vivo. Journal of immunology (Baltimore, Md. : 1950) 54 23872051
2018 YB-1 Expression and Phosphorylation Regulate Tumorigenicity and Invasiveness in Melanoma by Influencing EMT. Molecular cancer research : MCR 49 29743296
2001 Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 48 11390977
2022 YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy. Cells 47 35406781
2021 YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. Leukemia 44 34465866
2020 Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation. Nucleic acids research 41 32710623
2020 YB-3 substitutes YB-1 in global mRNA binding. RNA biology 40 31944153
2013 Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer. PloS one 40 24260353
2010 YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis. Biochemical and biophysical research communications 40 20599698
2024 PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer. Cell death discovery 39 38182573
2020 Ybx1 fine-tunes PRC2 activities to control embryonic brain development. Nature communications 39 32792512
2008 YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules. BMC biochemistry 38 18793384
2015 mRNA and DNA selection via protein multimerization: YB-1 as a case study. Nucleic acids research 35 26271991
2014 Calcineurin-mediated YB-1 dephosphorylation regulates CCL5 expression during monocyte differentiation. The Journal of biological chemistry 35 24947514
2023 FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1. EMBO reports 34 37489617
2020 Long non-coding RNA linc00665 interacts with YB-1 and promotes angiogenesis in lung adenocarcinoma. Biochemical and biophysical research communications 34 32423800
2019 YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway. Drug design, development and therapy 34 30679904
2019 Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus. Cells 34 31906126
2016 Therapeutic nuclear shuttling of YB-1 reduces renal damage and fibrosis. Kidney international 34 27591085
2015 YB-1 overexpression promotes a TGF-β1-induced epithelial-mesenchymal transition via Akt activation. Biochemical and biophysical research communications 33 25645014
2020 Y box binding protein 1 (YB-1) oncoprotein at the hub of DNA proliferation, damage and cancer progression. Biochimie 32 33058958
2017 YB-1 regulates tumor growth by promoting MACC1/c-Met pathway in human lung adenocarcinoma. Oncotarget 32 28624808
2012 YB-1 synthesis is regulated by mTOR signaling pathway. PloS one 30 23285076
2018 The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors. Oncotarget 29 29805738
2015 Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells. Oncotarget 29 26512918
2021 Long noncoding RNA HOTAIR interacts with Y-Box Protein-1 (YBX1) to regulate cell proliferation. Life science alliance 28 34266873
2020 YB-1 interplays with ERα to regulate the stemness and differentiation of ER-positive breast cancer stem cells. Theranostics 28 32206124
2020 YB-1: The key to personalised prostate cancer management? Cancer letters 28 32681926
2017 YB-1 expression promotes pancreatic cancer metastasis that is inhibited by microRNA-216a. Experimental cell research 28 28782557
2021 YB-1 unwinds mRNA secondary structures in vitro and negatively regulates stress granule assembly in HeLa cells. Nucleic acids research 27 34469566
2021 YBX1 Enhances Metastasis and Stemness by Transcriptionally Regulating MUC1 in Lung Adenocarcinoma. Frontiers in oncology 27 34976785
2005 YB-1 represses AP1-dependent gene transactivation and interacts with an AP-1 DNA sequence. The Biochemical journal 27 15702969
2019 The YB-1:Notch-3 axis modulates immune cell responses and organ damage in systemic lupus erythematosus. Kidney international 25 31882173
2016 ΔNp63α controls YB-1 protein stability: evidence on YB-1 as a new player in keratinocyte differentiation. Genes to cells : devoted to molecular & cellular mechanisms 25 27168020
2016 Cold shock protein YB-1 is involved in hypoxia-dependent gene transcription. Biochemical and biophysical research communications 24 27524241
2009 HSP60 interacts with YB-1 and affects its polysome association and subcellular localization. Biochemical and biophysical research communications 24 19470374
2021 Novel Insights into YB-1 Signaling and Cell Death Decisions. Cancers 23 34282755
2020 Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle. Cancers 23 32013098
2017 YB-1 orchestrates onset and resolution of renal inflammation via IL10 gene regulation. Journal of cellular and molecular medicine 23 28664613
2013 YB1 binds to and represses the p16 tumor suppressor gene. Genes to cells : devoted to molecular & cellular mechanisms 22 24165022
2011 YBX1 expression and function in early hematopoiesis and leukemic cells. Immunogenetics 22 21369783
2020 Tumour Progression Stage-Dependent Secretion of YB-1 Stimulates Melanoma Cell Migration and Invasion. Cancers 21 32824741
2018 YB-1 promotes laryngeal squamous cell carcinoma progression by inducing miR-155 expression via c-Myb. Future oncology (London, England) 21 29517281
2016 Nanog RNA-binding proteins YBX1 and ILF3 affect pluripotency of embryonic stem cells. Cell biology international 21 26289635
2016 Transportin-1-dependent YB-1 nuclear import. Biochemical and biophysical research communications 21 27794479
2013 Silencing the YB-1 gene inhibits cell migration in gastric cancer in vitro. Anatomical record (Hoboken, N.J. : 2007) 21 23613305
2024 Microglia-derived exosomes selective sorted by YB-1 alleviate nerve damage and cognitive outcome in Alzheimer's disease. Journal of translational medicine 20 38755651
2024 ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis. Nature communications 20 38782923
2023 Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1. Cell death & disease 20 37253771
2020 Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis. Acta biochimica et biophysica Sinica 20 32047913
2020 YB-1 Interferes with TNFα-TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNFα Signaling. International journal of molecular sciences 20 32992926
2017 The tumor-associated YB-1 protein: new player in the circadian control of cell proliferation. Oncotarget 20 28008157
2024 Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis. Journal of experimental & clinical cancer research : CR 18 38254206
2022 YB-1 Recruits Drosha to Promote Splicing of pri-miR-192 to Mediate the Proangiogenic Effects of H2S. Antioxidants & redox signaling 18 35044231
2022 YB-1 promotes cell proliferation and metastasis by targeting cell-intrinsic PD-1/PD-L1 pathway in breast cancer. The international journal of biochemistry & cell biology 18 36265523
2023 Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo. Cancer letters 17 37730104
2018 The Role of YB1 in Renal Cell Carcinoma Cell Adhesion. International journal of medical sciences 17 30275756
2013 YB-1 stabilizes HIV-1 genomic RNA and enhances viral production. Protein & cell 17 23589019
2021 YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation. International journal of molecular sciences 16 35008856
2020 YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation. Cancers 16 32764479
2020 Critical Role for Cold Shock Protein YB-1 in Cytokinesis. Cancers 15 32882852
2013 Tip110 interacts with YB-1 and regulates each other's function. BMC molecular biology 14 23822148
2002 Cloning of the gene encoding the decorin-binding protein B (DbpB) in Borrelia burgdorferi sensu lato and characterisation of the antibody responses to DbpB in Lyme borreliosis. Journal of medical microbiology 14 12171294
2024 YBX1: A Multifunctional Protein in Senescence and Immune Regulation. Current issues in molecular biology 13 39727969
2023 DNA binding protein YB-1 is a part of the neutrophil extracellular trap mediation of kidney damage and cross-organ effects. Kidney international 13 36963487
2022 Role of YB-1 Protein in Inflammation. Biochemistry. Biokhimiia 13 35501989
2016 Muramyl peptides activate innate immunity conjointly via YB1 and NOD2. Innate immunity 13 27694635
2015 Y-box binding protein 1 (YB-1) promotes detection of DNA bulky lesions by XPC-HR23B factor. Biochemistry. Biokhimiia 13 25756536
1993 Isolation of the CCAAT transcription factor subunit EFIA cDNA and a potentially functional EFIA processed pseudogene from Bos taurus: insights into the evolution of the EFIA/dbpB/YB-1 gene family. Gene 13 8444345
2018 YB-1 increases glomerular, but decreases interstitial fibrosis in CNI-induced nephropathy. Clinical immunology (Orlando, Fla.) 12 30018024

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