| 2001 |
YB-1 (p50) is a potent cap-dependent mRNA stabilizer; its cold shock domain mediates mRNA stabilization by competing with eIF4E for binding at or near the mRNA 5' cap, and YB-1 depletion accelerates mRNA decay in vitro and in vivo. |
In vitro mRNA stability assays, eIF4E cap-binding competition assays, YB-1 overexpression and depletion experiments |
The EMBO journal |
High |
11574481
|
| 2001 |
YB-1/p50 promotes rapid annealing of complementary RNA and DNA strands (up to 1500-fold acceleration) and can catalyze strand exchange; at low concentrations it promotes duplex formation, while excess YB-1 unwinds double-stranded forms. Phosphorylation selectively inhibits DNA annealing. |
In vitro nucleic acid annealing and strand-exchange assays across salt/temperature ranges; phosphorylation experiments |
The Journal of biological chemistry |
High |
11585833
|
| 2004 |
At low YB-1/mRNA ratios (polysomal), YB-1 binds mRNA as a monomer using both RNA-binding domains; at high ratios (untranslatable mRNPs), YB-1 forms multimeric complexes (~700 kDa, ~20 subunits) that pack ~600–700 nt of mRNA on their surface, correlating with translational repression. |
Atomic force microscopy, electron microscopy, biochemical sedimentation, in vitro complex reconstitution at defined YB-1:mRNA ratios |
Nucleic acids research |
High |
15494450
|
| 2006 |
Akt phosphorylates YB-1, and phospho-YB-1 fails to inhibit cap-dependent translation (but not IRES-dependent translation) of reporter mRNAs in vitro; Akt co-associates with inactive mRNPs and can relieve translational repression of YB-1-bound mRNAs. |
In vitro translation assays, co-immunoprecipitation of Akt with mRNPs, Affymetrix microarray identification of YB-1-associated mRNAs, phosphorylation-deficient mutant analysis |
Molecular and cellular biology |
High |
16354698
|
| 2005 |
YB-1 autoregulates its own translation by binding a specific element (UCCAG/ACAA motif) in the 3'UTR of its own mRNA, causing accumulation of free mRNPs and inhibiting translation at the initiation step; PABP competes with YB-1 for this element and restores translational activity. |
In vitro translation assays, RNA binding mapping (UCCAG/ACAA for YB-1, ~50-nt A-rich for PABP), mRNP sedimentation analysis |
Molecular and cellular biology |
High |
15798215
|
| 1995 |
YB-1 binds single-stranded DNA with higher affinity than double-stranded DNA at the MHC class II DRA promoter; it binds ssDNA at the X box and dsDNA at the Y box, and induces or stabilizes single-stranded regions in the promoter (detected by mung bean nuclease), consistent with a repression model that prevents loading of transactivating factors. |
EMSA with purified recombinant YB-1, methylation interference mapping, mung bean nuclease analysis, YB-1-specific antibodies on endogenous protein |
The Journal of biological chemistry |
High |
7876087
|
| 2005 |
YB-1 knockout mouse embryos show late embryonic lethality (after E13.5); YB-1−/− fibroblasts exhibit reduced stress responses, premature senescence under oxidative stress, and elevated CDK inhibitors p16Ink4a and p21Cip1; the senescence defect is rescued by siRNA knockdown of CDK inhibitors, indicating YB-1 normally represses CDK inhibitor transcription. |
Knockout mouse model, siRNA rescue experiments, stress assays, transcriptome/proteome profiling |
Molecular and cellular biology |
High |
15899865
|
| 2007 |
PP2Cgamma phosphatase interacts with YB-1 via its acidic domain to regulate alternative splicing of CD44 exons v4 and v5; PP2Cgamma phosphorylation enhances its interaction with YB-1, and PP2Cgamma knockdown affects CD44 alternative splicing in a YB-1-dependent manner. |
Co-IP, phosphatase activity assays in vitro splicing, siRNA knockdown, in vivo splicing assays |
Nature structural & molecular biology |
High |
17572683
|
| 2012 |
YB-1 binds CAUC and CACC motifs (defined by SELEX), which function as splicing enhancers; YB-1 activates exon inclusion at weak 3' splice sites by facilitating recruitment of U2AF65 to weak polypyrimidine tracts through direct protein–protein interaction with U2AF65. |
SELEX, in vivo splicing minigene assays, direct protein–protein interaction assays between YB-1 and U2AF65, endogenous CD44 exon v5 analysis |
Nucleic acids research |
High |
22730292
|
| 2008 |
YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro; electron and atomic force microscopy show that YB-1 coats the outer microtubule wall; YB-1 also promotes assembly of MAPs-tubulin and subtilisin-treated tubulin, and tubulin competes with RNA for YB-1 binding. |
In vitro microtubule assembly assays, electron microscopy, atomic force microscopy, direct binding assays |
BMC biochemistry |
High |
18793384
|
| 2009 |
YB-1 localizes to human mitochondria and contributes to mitochondrial mismatch repair (MMR) activity; YB-1 depletion significantly reduces mitochondrial mismatch-binding and MMR activity in HeLa cell extracts and increases mitochondrial DNA mutagenesis. |
Mitochondrial fractionation, mismatch-binding assays with mitochondrial extracts, siRNA depletion, mitochondrial DNA mutagenesis assay |
DNA repair |
High |
19272840
|
| 2015 |
Stress-induced tRNA-derived fragments (tRFs) from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) suppress oncogenic transcript stability by displacing 3'UTRs from YBX1 in a sequence-specific manner; the tRFs share a motif matching the YBX1 recognition sequence, and this displacement-based silencing suppresses breast cancer invasion and metastasis. |
RNA immunoprecipitation, LNA anti-sense inhibition, synthetic RNA mimetics, gain-/loss-of-function assays, in vivo metastasis models |
Cell |
High |
25957686
|
| 2015 |
YB-1 directly binds to and translationally activates the 5'UTR of HIF1A mRNA, increasing HIF1α protein expression in sarcoma cells, which drives invasion and metastasis via a YB-1–HIF1α axis. |
Direct RNA binding assays, translational reporter assays, loss-of-function in vitro and in vivo metastasis models |
Cancer cell |
High |
25965573
|
| 2015 |
YB-1 directly binds the 5'UTR of G3BP1 mRNA and translationally activates it, controlling G3BP1 availability for stress granule nucleation; YB-1 inactivation dramatically reduces G3BP1 protein levels and stress granule formation in sarcoma cells. |
Direct RNA binding (5'UTR), translational reporter assays, YB-1 inactivation with defined G3BP1/SG phenotype, in vivo xenograft models |
The Journal of cell biology |
High |
25800057
|
| 2015 |
HACE1 E3 ubiquitin ligase polyubiquitinates YB-1 through non-canonical K27-linked ubiquitin chains; these linkages are required for YB-1 interaction with TSG101 (MVB pathway component) and for its extracellular secretion. Secreted YB-1 inhibits TGF-β-mediated EMT. |
E3 ligase identification, ubiquitin chain-type analysis, Co-IP of YB-1 with TSG101, secretion assays, TGF-β functional assay |
Cellular signalling |
High |
26343856
|
| 2019 |
Class I HDAC inhibitor MS-275 promotes acetylation of YB-1 at lysine-81, blocking YB-1 binding to 5'UTRs of NFE2L2 (NRF2), HIF1A, and G3BP1 mRNAs and reducing their translation; a YB-1(K81A) mutant resistant to acetylation restores metastatic capacity and target protein synthesis. |
Global acetylomics, site-directed mutagenesis (K81A), 5'UTR binding assays, translational assays, in vivo metastasis rescue |
EMBO reports |
High |
31668005
|
| 2020 |
YBX1 is a target of JAK2 phosphorylation; inactivation of YBX1 in JAK2V617F cells causes RNA mis-splicing (intron retention), disrupts transcriptional control of ERK signaling, and sensitizes persisting cells to apoptosis; combined JAK inhibition + YBX1 inactivation induces molecular remission in mouse models. |
In-depth phosphoproteome profiling, genetic inactivation, RNA splicing analysis, in vivo JAK2-mutated mouse models, primary human cells |
Nature |
High |
33239784
|
| 2020 |
The structural basis of YB-1 CSD DNA binding was determined; the C-terminal extension of the CSD adopts a rigid structure interacting with core CSD residues and provides a unique DNA binding site. Phosphorylation of S102 destabilizes the CSD, causes partial unfolding, and dramatically reduces ssDNA binding affinity. |
Crystal structure of YB-1 CSDex, NMR, ssDNA binding assays, phosphomimetic and deletion mutants |
Nucleic acids research |
High |
32710623
|
| 2021 |
YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells; YBX1 condensates selectively recruit miR-223 in vitro and promote its sorting into exosomes. Point mutations that inhibit LLPS impair YBX1 incorporation into condensates and perturb miR-223 sorting into exosomes. |
In vitro LLPS assays, live-cell imaging of condensates, miRNA sorting assays, LLPS-deficient point mutants, exosome isolation |
eLife |
High |
34766549
|
| 2021 |
YBX1 promotes translation of oncogenic transcripts including MYC by recruitment to polysomal chains; genetic inactivation of YBX1 in AML cells displaces MYC and other oncogenic drivers from polysomes, depleting their protein levels and reducing leukemia cell fitness. |
Ribosome/polysome profiling, genetic inactivation (KO), protein level analysis, in vitro and in vivo competition assays |
Leukemia |
High |
34465866
|
| 2013 |
YB-1 disrupts MutSα (MSH2-MSH6) MMR complex formation by interacting with PCNA via two PIP-box motifs in its C-terminal domain; this interaction reduces MutSα mismatch-binding activity, disrupts MutSα/PCNA/heteroduplex ternary complex formation, and inhibits in vitro MMR activity. YB-1 overexpression is associated with microsatellite instability and increased mutation rates. |
In vitro MMR assays, PIP-box mutagenesis, Co-IP, PCNA interaction mapping, microsatellite instability assays, mutation frequency measurements |
Oncogene |
High |
24141788
|
| 2016 |
Transportin-1 mediates YB-1 nuclear import; YB-1/transportin-1 complex is isolated from HeLa extracts; nuclear import is abolished by a competitor substrate or transportin-1 inhibitor M9M but not by importin-β1 inhibitors; inactivating mutations in a transportin-1-dependent NLS (P201A/Y202A) abolish transport. |
Co-immunoprecipitation from cell extracts, in vitro nuclear import assay, competitor/inhibitor experiments, NLS point mutagenesis |
Biochemical and biophysical research communications |
High |
27794479
|
| 2020 |
YB-1 nuclear localization is cell-cycle regulated: YB-1 is perinuclear during G1/S and enters the nucleus during late G2/M, exiting at mitosis completion. Dephosphorylation at S102, S165, and S176 increases accessibility of the NLS (shown by MD simulations), facilitating nuclear entry; no proteolytic cleavage is required. |
Live-cell confocal imaging, mass spectrometry of phosphorylation sites, atomistic MD simulations, doxorubicin-induced G2 arrest |
Cancers |
High |
32013098
|
| 2020 |
Phospho-YB-1 (S102) cytoplasmic YB-1 directly stabilizes Col1a1 mRNA, promoting fibrosis; forced nuclear compartmentalization of phosphorylated YB-1 by small molecule HSc025 instead represses the Col1a1 promoter and attenuates fibrosis in vivo. |
Yb1+/- mouse model of unilateral ureteral obstruction, phospho-specific antibodies, mRNA stability assays, pharmacological nuclear shuttling with HSc025 |
Kidney international |
High |
27591085
|
| 2020 |
CircRNA-SORE binds YBX1 in the cytoplasm, preventing its interaction with the E3 ubiquitin ligase PRP19 and thus blocking PRP19-mediated YBX1 ubiquitination and degradation, thereby stabilizing YBX1 protein. |
RNA pulldown, Co-IP, PRP19 ubiquitination assays, circRNA knockdown in vitro and in vivo |
Signal transduction and targeted therapy |
High |
33361760
|
| 2018 |
Ionizing radiation and EGF induce RSK (p90 ribosomal S6 kinase) nuclear translocation, where RSK phosphorylates already-nuclear YB-1 at Ser-102; acute stimulation does not cause cytoplasm-to-nucleus translocation of YB-1 itself. In KRAS-mutant cells, YB-1 is constitutively phosphorylated. |
Nuclear/cytoplasmic fractionation, phospho-specific antibodies, pharmacological RSK/EGFR inhibitors, conditional KRAS(G12V) expression |
International journal of molecular sciences |
High |
30126195
|
| 2019 |
Inhibition of RNA polymerase II triggers phosphorylation of YB-1 at Ser102 and its nuclear accumulation; kinase inhibition reduces both phosphorylation and nuclear accumulation; nuclear RNA presence is required for nuclear retention of YB-1. |
RNAPII inhibitors, kinase inhibitors, nuclear fractionation, immunofluorescence, RNA depletion experiments |
Cells |
High |
31906126
|
| 2015 |
Poly(ADP-ribose)polymerase 1 (PARP1) poly(ADP-ribosyl)ates YB-1 in the presence of damaged DNA in vitro, identifying PARylation as a novel post-translational modification of YB-1 linked to the DNA damage response. |
In vitro PARylation assay with PARP1, damaged DNA substrate, Western blot for PAR-modified YB-1 |
Biochimie |
Medium |
26453809
|
| 2014 |
Calcineurin (CN) dephosphorylates YB-1 at Ser-102, preventing phospho-YB-1 binding to and transactivation of the CCL5 promoter during monocyte differentiation. Phospho-YB-1(Ser-102), generated via Akt, shows stronger CCL5 promoter binding; CN directly interacts with YB-1 (demonstrated by Co-IP). |
Co-IP of YB-1/calcineurin, phosphatase assay, ChIP on CCL5 promoter, pharmacological calcineurin inhibition (cyclosporine A) in vivo |
The Journal of biological chemistry |
High |
24947514
|
| 2017 |
YB-1 interacts directly with Smad2 and stabilizes it by attenuating Smad2 ubiquitination; Smad2 acts as a transcription factor that activates the YB-1 promoter, forming a positive feedback loop. Ser102 phosphorylation of YB-1 is required for both its binding to and stabilization of Smad2. |
Co-IP, ubiquitination assays, promoter reporter assays, YB-1 Ser102 mutagenesis, in vivo CCl4 liver fibrosis model |
Biochemical and biophysical research communications |
Medium |
28153731
|
| 2017 |
YB-1 and cytosolic NSUN2 are the only proteins in HEK293 cytosolic extract that specifically recognize three structural RNA motifs (ACCAGCCU, CAGUGAGC, UAAUCCCA) enriched in exosomal mRNAs, as shown by pull-down with RNA hairpins; both proteins are found in exosomes. |
RNA hairpin pull-down from cytosolic extract, mass spectrometry identification, exosome isolation and protein detection |
Biochimica et biophysica acta. Proteins and proteomics |
Medium |
28341602
|
| 2017 |
YBX1 is required for sorting of multiple small ncRNA species (miRNAs, tRNAs, Y RNAs, Vault RNAs) into exosomes, as demonstrated by TGIRT-seq of immunoisolated CD63+ exosomes from YBX1-depleted HEK293T cells. |
TGIRT-seq, flotation gradient ultracentrifugation, CD63 immunoisolation of exosomes, YBX1 knockdown |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29073095
|
| 2002 |
In human myxoid liposarcoma cells, wild-type TLS binds to YB-1 through its C-terminal domain and cooperates with YB-1 to promote RNA splicing (13S isoform of adenovirus E1A pre-mRNA). The oncogenic TLS/CHOP fusion protein lacks the ability to recruit YB-1 and inhibits YB-1-mediated splicing in a dominant-negative manner. |
Co-IP of TLS and YB-1, in vivo splicing assay with adenovirus E1A minigene, TLS/CHOP dominant-negative analysis |
Journal of orthopaedic research |
Medium |
12168660
|
| 2001 |
YB-1 (dbpB) is proteolytically cleaved from mRNA upon thrombin stimulation of endothelial cells, releasing an active ~30 kDa species that translocates to the nucleus and activates thrombin-responsive gene transcription; cytosolic full-length dbpB is mRNA-bound, and RNase treatment of cytosolic extracts activates it. |
Oligo(dT) affinity chromatography, Nycodenz gradient fractionation, RNase treatment, reporter transfection assays, immunoprecipitation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11390977
|
| 2000 |
YB-1 co-immunoprecipitates with FMRP (fragile X mental retardation protein) and is identified as a component of the FMRP-associated mRNP complex by mass spectrometry. |
Co-immunoprecipitation from Flag-Fmr1 stable cell lines, mass spectrometry identification, anti-p50 antibody confirmation |
Biochemical and biophysical research communications |
Medium |
11162447
|
| 2008 |
MBNL1 forms an RNP complex with YB-1 and DDX1 (demonstrated by GST pulldown); under stress, MBNL1 co-localizes with YB-1 at cytoplasmic stress granules. |
GST pulldown, co-immunoprecipitation, stress granule co-localization by immunofluorescence |
Journal of neuroscience research |
Medium |
18335541
|
| 2005 |
Nuclear YB-1 selectively inhibits p53's ability to cause cell death and to transactivate cell death genes, but does not interfere with p53-mediated transactivation of CDKN1A (p21) or MDM2; transcriptionally active p53 is required for nuclear localization of YB-1. |
Co-expression experiments, transcriptional reporter assays for p53 target genes, cell death assays, mammary epithelial cell p53 stress activation |
Oncogene |
Medium |
16158057
|
| 2011 |
YB-1 localizes to the centrosome in a phosphorylation-dependent manner, where it complexes with pericentrin and γ-tubulin, maintaining structural integrity and microtubule nucleation capacity; YB-1 overexpression in mammary epithelial cells causes cytokinesis failure and centrosome amplification. |
Antibody microarray, co-immunoprecipitation of YB-1 with pericentrin and γ-tubulin, centrosome localization imaging, conditional YB-1 expression in HMECs |
Oncogene |
Medium |
21423216
|
| 2020 |
YB-1 depletion causes cytokinesis failure and multinucleation; phosphorylation at six serine residues (including novel sites identified by mass spectrometry) is required for cytokinesis; YB-1 orchestrates spatio-temporal distribution of microtubules, β-actin, and the chromosome passenger complex (CPC) to define the cleavage plane. |
siRNA depletion with rescue, confocal imaging of cytokinesis structures, mass spectrometry for phosphorylation sites, atomistic MD modelling |
Cancers |
High |
32882852
|
| 2015 |
Phosphorylated YB-1 accumulates in the centrosome at mitotic phase; YB-1 knockdown causes microtubule detachment from the centrosome at telophase and nuclear lobulation due to defective nuclear envelope reassembly from mis-localized non-centrosomal microtubules. |
YB-1 knockdown, immunofluorescence of centrosomal YB-1, microtubule localization analysis, nuclear morphology assays |
Scientific reports |
Medium |
25740062
|
| 2021 |
YB-1 unwinds mRNA secondary structures without ATP consumption via its conserved CSD (which destabilizes RNA stem/loops) and its unstructured C-terminal domain (which secures unwinding); at endogenous levels YB-1 facilitates stress granule disassembly after stress recovery; overexpression inhibits stress granule assembly. |
In vitro RNA unwinding assays, CSD mutagenesis, live-cell imaging of stress granules in YB-1 KO and overexpressing cells, arsenite stress |
Nucleic acids research |
High |
34469566
|
| 2004 |
YB-1 physically associates with Sox21 and partially restores NGF-induced neurite outgrowth inhibited by Sox21 overexpression in PC12 cells, indicating YB-1 can antagonize Sox21-mediated repression of neuronal differentiation. |
Co-immunoprecipitation of endogenous proteins, neurite outgrowth rescue assay |
Neuroscience letters |
Low |
15039105
|
| 2017 |
YBX1 phosphorylation at Ser-176, identified by mass spectrometry, is required for NF-κB activation; YBX1-S176A mutant shows dramatically reduced NF-κB-activating ability compared to WT, and Ser-176 and Ser-165 regulate distinct subsets of NF-κB target genes. |
Mass spectrometry identification of S176 phosphosite, S176A mutagenesis, NF-κB reporter assays |
The Journal of biological chemistry |
Medium |
28077578
|
| 2022 |
RSK2-mediated phosphorylation of YB-1 at Ser102 promotes formation of a YB-1/KLF5 transcriptional complex; this complex co-regulates expression of KRT16 and Ly6D to promote basal-like breast cancer proliferation. YB-1 also stabilizes KLF5 mRNA in an RNA 5-methylcytosine modification-dependent manner. |
Co-IP of YB-1/KLF5, RSK2 kinase assays, m5C modification assays, ChIP-seq, luciferase reporters, RSK inhibitor LJH685 in vivo |
Cell death and differentiation |
High |
35022570
|
| 2022 |
CircIPO7 binds YBX1 protein in the cytoplasm, facilitates its phosphorylation at Ser102 by AKT, and promotes YBX1 nuclear translocation, leading to transcriptional activation of FGFR1, TNC, and NTRK1. |
RNA-protein pulldown, Co-IP, nuclear fractionation, phosphorylation assays, luciferase reporter assays, in vitro and in vivo metastasis assays |
Clinical cancer research |
Medium |
35917517
|
| 2012 |
YB-1 mRNA translation is regulated by the mTOR signaling pathway; specific mTOR inhibition with PP242 (but not rapamycin) suppresses YB-1 synthesis; this dependence is dictated by the 5'UTR of YB-1 mRNA (shown by reporter constructs). |
Western/Northern blotting, mTOR inhibitor (PP242 vs. rapamycin) treatment, 5'UTR reporter constructs |
PloS one |
Medium |
23285076
|
| 2025 |
YBX1 binds to m5C modification sites in the RNF115 mRNA 3'UTR and interacts with EIF4A1 to bridge the 5'UTR, promoting mRNA circularization and translation of RNF115; NSUN2 is responsible for m5C modification of RNF115 mRNA; YBX1-driven RNF115 translation suppresses ferroptosis via DHODH ubiquitination. |
RIP-seq, ribosome sequencing, bisulfite sequencing, Co-IP mass spectrometry, RNA pulldown, MeRIP-qPCR, dual-luciferase reporter, xenograft models |
Clinical and translational medicine |
High |
40088428
|
| 2024 |
ZO-1 interacts with YB-1 in endothelial cells; arsenite-induced stress decreases ZO-1/YB-1 interaction and drives stress granule assembly; YB-1 expression is essential for stress granule formation and for cytoprotective effects induced by ZO-1 downregulation; endothelial-specific ZO-1 deletion increases YB-1-positive granules in retinal vessels and alters angiogenesis. |
Proteome-wide interactome, Co-IP, live-cell imaging, endothelial-specific conditional KO mice, retinal vascular imaging |
Nature communications |
High |
38782923
|
| 2020 |
YBX1 controls thermogenic adipocyte differentiation (browning) in white adipose tissue; YBX1 knockdown impairs thermogenic potential of brown and brite preadipocytes; CRISPRa-induced YBX1 expression promotes browning; transcriptomic analysis shows YBX1 regulates the histone H3K9 demethylase Jmjd1c to promote thermogenic commitment. |
Temporal proteomics of cold-exposed scWAT, siRNA KD, CRISPRa induction, transcriptomic analysis, mitochondrial respiration assays |
Molecular metabolism |
Medium |
33285300
|