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Y-box binding protein 1 OKDB#: 1294
 Symbols: YBX1, YB1 Species: human
 Synonyms: YB1, BP-8, CSDB, DBPB, YB-1, CBF-A, CSDA2, EFI-A, NSEP1, NSEP-1, MDR-NF1  Locus: 1p34.2 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment The expression of HLA class II genes is regulated by a series of cis-acting elements and transacting factors. Several cis-acting elements have been identified and have been termed the Z box, X box, Y box, octamer, and 'TATA' box. The Y box contains an inverted CCAAT box. Didier et al. (1988) isolated a cDNA encoding a Y box-binding protein designated YB1, or NSEP1. YB1 binding has an absolute requirement for the CCAAT box and relative specificity for the Y box. It has a molecular mass of 35,414 and contains 18% basic residues and putative nuclear localization signals.

NCBI Summary: This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Sep 2015]
General function Nucleic acid binding, DNA binding, Transcription factor, RNA binding
Comment
Cellular localization Nuclear
Comment Knock123 ///////Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1. Wang X et al. (2020) The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA damage repair and promoted apoptosis of GCs. Mechanistically, we discovered that HCP5 stabilized the interaction between YB1 and its partner ILF2, which could mediate YB1 transferring into the nucleus of GCs. HCP5 silencing affected the localization of YB1 into nucleus and reduced the binding of YB1 to the promoter of MSH5 gene, thereby diminishing MSH5 expression. Taken together, we identified that the decreased expression of HCP5 in bPOI contributed to dysfunctional GCs by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.//////////////////
Ovarian function Steroid metabolism, Oogenesis, Oocyte maturation, Early embryo development
Comment Extracellular signal-regulated kinase (ERK)-dependent phosphorylation of Y-Box binding protein 1 (YB-1) enhances gene expression in granulosa cells in response to follicle stimulating hormone (FSH). Donaubauer EM et al. (2016) Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs by FSH leads to their proliferation and differentiation, events that are necessary for fertility. FSH activates multiple signaling pathways to regulate genes necessary for follicular maturation. Herein, we investigated the role of Y-box binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein that regulates transcription and translation. Our results show that FSH promotes an increase in the phosphorylation of YB-1 on Ser(102)within 15 min that is maintained at significantly increased levels until ~8 h post treatment. FSH-stimulated phosphorylation of YB-1(Ser(102)) is prevented by pretreatment of GCs with the PKA-selective inhibitor PKI, the MEK inhibitor PD98059, or the ribosomal S6 kinase-2 (RSK-2) inhibitor BI-D1870. Thus phosphorylation of YB-1 on Ser(102)is PKA, ERK, and RSK-2 dependent. However, pretreatment of GCs with the protein phosphatase 1 (PP1) inhibitor tautomycin increased phosphorylation of YB-1(Ser(102)) in the absence of FSH; FSH did not further increase YB-1(Ser(102)) phosphorylation. This result suggests that the major effect of RSK-2 is to inhibit PP1 rather than to directly phosphorylate YB-1 on Ser(102) YB-1 coimmunoprecipitated with PP1β catalytic subunit and RSK-2. Transduction of GCs with the dephospho-adenoviral(Ad)-YB-1(S102A) mutant prevented the induction by FSH ofEgfr, Cyp19a1, Inha, Lhcgr, Cyp11a1, Hsd17b1, andPappamRNAs and estradiol-17β production. Collectively, our results reveal that phosphorylation of YB-1 on Ser(102)via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated expression of target genes required for maturation of follicles to a preovulatory phenotype.//////////////////
Expression regulated by FSH
Comment Notch signaling regulates differentiation and steroidogenesis in female mouse ovarian granulosa cells. Prasasya RD et al. (2017) The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. While Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the LH-receptor in prepubertal mouse ovary. JAG1, the most abundantly expressed Notch ligand in mouse ovary, revealed a striking shift in localization from oocytes to somatic cells following hormone stimulation. Using primary cultures of granulosa cells, we investigated the functions of Jag1 using siRNA knockdown. The loss of JAG1 led to suppression of granulosa cell differentiation as marked by reduced expression of enzymes and factors involved in steroid biosynthesis, and in steroid secretion. Jag1 knockdown also resulted in enhanced cell proliferation. These phenotypes were replicated, although less robustly, following knockdown of the obligate canonical Notch transcription factor RBPJ. Intracellular signaling analysis revealed increased activation of the mitogenic PI3K/AKT and MAPK/ERK pathways following Notch knockdown, with a MEK inhibitor blocking the enhanced proliferation observed in Jag1 knockdown granulosa cells. Activation of YB-1, a known regulator of granulosa cell differentiation genes was suppressed by Jag1 knockdown. Overall, this study reveals a role of Notch signaling in promoting the differentiation of preovulatory granulosa cells, adding to the diverse functions of Notch in the mammalian ovary.//////////////////
Ovarian localization Oocyte, Granulosa
Comment
Follicle stages Antral, Preovulatory
Comment Liu HC, et al 2001 reported tha application of complementary DNA microarray (DNA chip) technology in the study of gene expression profiles during folliculogenesis. They used oligonucleotide microarray (DNA chip)-based hybridization analysis to gain a comprehensive view of gene expression and regulation involved in folliculogenesis. Preantral follicles isolated from day 14 B6D2F-1 mice were stimulated in vitro to form Graafian follicles. Total RNA extracted from the mouse preantral and Graafian follicles were reverse transcribed, labeled with digoxigenin-11-dUTP, and then hybridized with Clontech Atlas mouse cDNA expression arrays for comparison. Of 588 known studied genes, 39 and 61 were detected in preantral follicles and in Graafian follicles, respectively, and 17 were highly expressed consistently in both preantral and Graafian follicles. Performing clustering analysis, 46 were upregulated as the follicles advanced to mature stages. The YB1 is up-regulated in the Graafian follicles.
Phenotypes
Mutations 1 mutations

Species: other
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Maternal Ybx1 safeguards zebrafish oocyte maturation and maternal-to-zygotic transition by repressing global translation. Sun J et al. (2018) Maternal mRNAs and proteins dictate early embryonic development before zygotic genome activation. In the absence of transcription, elaborate control of maternal mRNA translation is of particular importance for oocyte maturation and early embryogenesis. By analyzing zebrafish ybx1 mutants with a null allele, we demonstrate an essential role of maternal ybx1 in repressing global translation in oocytes and embryos. Loss of maternal Ybx1 leads to impaired oocyte maturation and egg activation. Maternal ybx1 (Mybx1) mutant embryos fail to undergo normal cleavage and the maternal-to-zygotic transition (MZT). Morpholino knockdown of ybx1 also results in MZT loss and epiboly failure, suggesting the post-fertilization requirement of Ybx1. Additionally, elevated global translation level and the unfolded protein response were found in Ybx1-depleted embryos. Supplementing translational repression by eIF4E inhibition markedly rescues the Mybx1 phenotype. Mechanistically, Ybx1 in embryos may associate with processing body (P-body) components and represses translation when tethered to target mRNAs. Collectively, our results identify maternal Ybx1 as a global translational repressor required for oocyte maturation and early embryogenesis.//////////////////

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Phenotypes and GWAS show phenotypes and GWAS
Links
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created: Sept. 13, 2001, 1:19 p.m. by: hsueh   email:
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last update: March 24, 2020, 2:08 p.m. by: hsueh    email:



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