Disease relevance of Ybx1

• Recombinant cDNA clones that express ORE-binding proteins were isolated from a mouse hepatoma expression library and found to be representatives of two different members of the murine Y-box family of transcription factors [1].
• Recombination hot spot of hepatitis B virus genome binds to members of the HMG domain protein family and the Y box binding protein family; implication of these proteins in genomic instability [2].
• The diverse biological roles of these Y-box proteins range from the control of the E. coli cold-shock stress response to the translational masking of messenger RNA in vertebrate gametes [3].
• Adenovirus-mediated YB-1 expression under the control of the COL1A2 enhancer significantly decreased COL1A2 promoter activity after carbon tetrachloride injection and subsequently suppressed the progression of hepatic fibrosis [4].
• METHODS: Recombinant adenoviruses expressing either green fluorescent protein or a transforming growth factor beta/Smad signal repressor, YB-1, were injected into mice untreated or treated with carbon tetrachloride [4].
• The Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers [5].

High impact information on Ybx1

• NF-Y is a sequence-specific DNA-binding protein that recognizes the Y box, a promoter element common to all major histocompatibility complex class II genes [6].
• Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response [7].
• Chromatin precipitation assays reveal that most of the MSY2 target mRNAs are transcribed from genes containing the Y-box DNA-binding motif in their promoters [8].
• Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation [9].
• Furthermore, when EC cytosolic extracts were subjected to Nycodenz gradient centrifugation, latent dbpB fractionated with mRNA, whereas active dbpB fractionated with free proteins [9].

Biological context of Ybx1

• The Y-box motif mediates redox-dependent transcriptional activation in mouse cells [1].
• We find that the mouse genome contains many DNA sequences with homology to a cDNA encoding the DNA-binding domain of the Y-box proteins [10].
• A processed pseudogene from Mus musculus, designated psi MSY-2, was obtained with a MSY-1 cDNA (encoding mouse Y-box factor 1) probe [10].
• In a search for interacting co-factors, a nuclear ankyrin-like repeat protein CARP (cardiac ankyrin repeat protein) was isolated from a rat neonatal heart cDNA library by yeast two-hybrid screening, using YB-1 as the bait [11].
• Additional experiments indicated that Pur alpha, Pur beta, and MSY1 also interact specifically, albeit weakly, with double-stranded DNA and with transcription enhancer factor-1 [12].

Anatomical context of Ybx1

• Mammalian male and female germ cells express a germ cell-specific Y-Box protein, MSY2 [13].
• RNA-binding proteins in mouse oocytes and embryos: expression of genes encoding Y box, DEAD box RNA helicase, and polyA binding proteins [14].
• Co-immunoprecipitation and GST-CARP pulldown studies reveal that CARP forms a physical complex with YB-1 in cardiac myocytes and immunostaining shows that endogenous CARP is localized in the cardiac myocyte nucleus [11].
• Cryptic MCAT enhancer regulation in fibroblasts and smooth muscle cells. Suppression of TEF-1 mediated activation by the single-stranded DNA-binding proteins, Pur alpha, Pur beta, and MSY1 [12].
• Mutations that selectively impaired high affinity single-stranded DNA binding by fibroblast or smooth muscle cell-derived Pur alpha, Pur beta, and MSY1 in vitro, released the cryptic MCAT enhancer from repression in transfected cells [12].

Associations of Ybx1 with chemical compounds

• DNA binding studies revealed that the core MCAT sequence mediates binding of transcription enhancer factor-1 to the double-stranded polypurine-polypyrimidine element while flanking nucleotides account for interaction of Pur alpha and Pur beta with the purine-rich strand and MSY1 with the complementary pyrimidine-rich strand [12].
• Here we demonstrate that association of YB-1 with the capped 5' terminus of the mRNA is regulated via phosphorylation by the serine/threonine protein kinase Akt [15].
• Moreover, both Pur proteins interact with MSY1, a VACssBF1-like protein cloned by virtue of its affinity for the pyrimidine-rich strand of the enhancer [16].
• We report the sequences of two coordinately induced murine glutathione transferase genes, mGSTM1 (GT8.7, Yb1) and mGSTM3 (GT9.3) [17].
• Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C [18].

Physical interactions of Ybx1

• In transgenic mice, mRNAs encoding exogenous GFP are directed or not directed into the MSY2-bound fraction by promoters containing or lacking the Y-box motif, respectively [8].
• The transcription factor PU.1 actively inhibits the expression of I-A beta through the binding to a DNA sequence near the Y box, a cis-element in the promoter necessary for transcription [19].
• Our results further indicate that the Xenopus Y box-binding proteins bind to an element 5' to the mouse protamine 2 gene [20].
• Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif [21].
• Mobility shift assays, Southwestern blots, and immunoprecipitation studies have established that this putative Y box binds a 52-kDa mouse testicular homologue of the Xenopus germ cell-specific Y-box protein and a competing 50-kDa protein present in both liver and testis nuclear extracts [22].

Regulatory relationships of Ybx1

• YB-1(-/-) cells under oxidative stress expressed high levels of the G(1)-specific CDK inhibitors p16Ink4a and p21Cip1 and senesced prematurely; this defect was corrected by knocking down CDK inhibitor levels with specific small interfering RNAs [23].

Other interactions of Ybx1

• In this study we used the yeast three-hybrid system to clone Msy4, which encodes a novel member of the Y box family of nucleic acid binding proteins [24].
• Zygotic transcription of MSY1 and RCK/p54 is evident in four-cell stage embryos [14].
• Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1 [25].
• Translational repression of protamine 1 (Prm1) mRNA requires sequences present in its 3' untranslated region (UTR) and substantial evidence suggests a role for the murine Y-box protein MSY4 in this process [26].
• Moreover, the cap-dependent repressor activity of YB-1 appears to be negatively regulated via Akt-mediated phosphorylation of the Ser-102 residue of YB-1 [27].

Analytical, diagnostic and therapeutic context of Ybx1

• Western blot analysis followed by semiquantitation by laser scanning showed the Ya, Yb1, Yb2, Yc, Yk, mu, and B1 subunits to be suppressed by 11, 11, 44, 30, 12, 14, and 47%, respectively, by interferon treatment [28].
• Immunohistologic analysis revealed nuclear localization of Purbeta and MSY1 particularly in fibrotic areas of the allograft myocardium demonstrating extravascular accumulation of VSM alpha-actin [29].
• Reporter and electrophoretic mobility shift assays revealed that the proximal GATA element in 5'-UTR region of YB-1 gene functions positively in K562 cells [30].
• Northern blot analysis revealed that YB-1(+/-) ES cells with one intact allele contain approximately one-half the amount of mRNA detected in wild-type (YB-1(+/+)) cells [18].
• Oligo(dT) affinity chromatography revealed that cytosolic dbpB from control EC, but not active dbpB from thrombin-treated EC, was bound to mRNA [9].

References