| 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
|