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Gene Review

Ybx1  -  Y box protein 1

Mus musculus

Synonyms: 1700102N10Rik, C79409, CBF-A, CCAAT-binding transcription factor I subunit A, DBPB, ...
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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


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


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


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].


  1. The Y-box motif mediates redox-dependent transcriptional activation in mouse cells. Duh, J.L., Zhu, H., Shertzer, H.G., Nebert, D.W., Puga, A. J. Biol. Chem. (1995) [Pubmed]
  2. 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. Kajino, K., Yamamoto, T., Hayashi, J., Umeda, T., Takahara, T., Hino, O. Intervirology (2001) [Pubmed]
  3. Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins. Wolffe, A.P. Bioessays (1994) [Pubmed]
  4. Cell type-specific intervention of transforming growth factor beta/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice. Inagaki, Y., Kushida, M., Higashi, K., Itoh, J., Higashiyama, R., Hong, Y.Y., Kawada, N., Namikawa, K., Kiyama, H., Bou-Gharios, G., Watanabe, T., Okazaki, I., Ikeda, K. Gastroenterology (2005) [Pubmed]
  5. Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Basaki, Y., Hosoi, F., Oda, Y., Fotovati, A., Maruyama, Y., Oie, S., Ono, M., Izumi, H., Kohno, K., Sakai, K., Shimoyama, T., Nishio, K., Kuwano, M. Oncogene (2007) [Pubmed]
  6. A multiplicity of CCAAT box-binding proteins. Dorn, A., Bollekens, J., Staub, A., Benoist, C., Mathis, D. Cell (1987) [Pubmed]
  7. Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response. Sorokin, A.V., Selyutina, A.A., Skabkin, M.A., Guryanov, S.G., Nazimov, I.V., Richard, C., Th'ng, J., Yau, J., Sorensen, P.H., Ovchinnikov, L.P., Evdokimova, V. EMBO J. (2005) [Pubmed]
  8. The DNA/RNA-binding protein MSY2 marks specific transcripts for cytoplasmic storage in mouse male germ cells. Yang, J., Medvedev, S., Reddi, P.P., Schultz, R.M., Hecht, N.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation. Stenina, O.I., Shaneyfelt, K.M., DiCorleto, P.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Isolation of a potentially functional Y-box protein (MSY-1) processed pseudogene from mouse: evolutionary relationships within the EF1A/dbpB/YB-1 gene family. Familari, M., Almouzni, G., Wolffe, A.P. Gene (1994) [Pubmed]
  11. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Zou, Y., Evans, S., Chen, J., Kuo, H.C., Harvey, R.P., Chien, K.R. Development (1997) [Pubmed]
  12. 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. Carlini, L.E., Getz, M.J., Strauch, A.R., Kelm, R.J. J. Biol. Chem. (2002) [Pubmed]
  13. Mammalian male and female germ cells express a germ cell-specific Y-Box protein, MSY2. Gu, W., Tekur, S., Reinbold, R., Eppig, J.J., Choi, Y.C., Zheng, J.Z., Murray, M.T., Hecht, N.B. Biol. Reprod. (1998) [Pubmed]
  14. RNA-binding proteins in mouse oocytes and embryos: expression of genes encoding Y box, DEAD box RNA helicase, and polyA binding proteins. Paynton, B.V. Dev. Genet. (1998) [Pubmed]
  15. Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Evdokimova, V., Ruzanov, P., Anglesio, M.S., Sorokin, A.V., Ovchinnikov, L.P., Buckley, J., Triche, T.J., Sonenberg, N., Sorensen, P.H. Mol. Cell. Biol. (2006) [Pubmed]
  16. Molecular interactions between single-stranded DNA-binding proteins associated with an essential MCAT element in the mouse smooth muscle alpha-actin promoter. Kelm, R.J., Cogan, J.G., Elder, P.K., Strauch, A.R., Getz, M.J. J. Biol. Chem. (1999) [Pubmed]
  17. The structure of two murine class-mu glutathione transferase genes coordinately induced by butylated hydroxyanisole. Reinhart, J., Pearson, W.R. Arch. Biochem. Biophys. (1993) [Pubmed]
  18. 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. Shibahara, K., Uchiumi, T., Fukuda, T., Kura, S., Tominaga, Y., Maehara, Y., Kohno, K., Nakabeppu, Y., Tsuzuki, T., Kuwano, M. Cancer Sci. (2004) [Pubmed]
  19. Repression mechanisms of the I-A beta gene of the major histocompatibility complex. Lloberas, J., Soler, C., Celada, A. Immunobiology (1997) [Pubmed]
  20. A mouse homologue of the Xenopus germ cell-specific ribonucleic acid/deoxyribonucleic acid-binding proteins p54/p56 interacts with the protamine 2 promoter. Nikolajczyk, B.S., Murray, M.T., Hecht, N.B. Biol. Reprod. (1995) [Pubmed]
  21. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Collart, M.A., Baeuerle, P., Vassalli, P. Mol. Cell. Biol. (1990) [Pubmed]
  22. Deoxyribonucleic acid-protein interactions associated with transcriptional initiation of the mouse testis-specific cytochrome c gene. Yiu, G.K., Murray, M.T., Hecht, N.B. Biol. Reprod. (1997) [Pubmed]
  23. YB-1 is important for late-stage embryonic development, optimal cellular stress responses, and the prevention of premature senescence. Lu, Z.H., Books, J.T., Ley, T.J. Mol. Cell. Biol. (2005) [Pubmed]
  24. A sequence-specific RNA binding complex expressed in murine germ cells contains MSY2 and MSY4. Davies, H.G., Giorgini, F., Fajardo, M.A., Braun, R.E. Dev. Biol. (2000) [Pubmed]
  25. Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1. Ohba, H., Chiyoda, T., Endo, E., Yano, M., Hayakawa, Y., Sakaguchi, M., Darnell, R.B., Okano, H.J., Okano, H. Neurosci. Lett. (2004) [Pubmed]
  26. Translational repression by MSY4 inhibits spermatid differentiation in mice. Giorgini, F., Davies, H.G., Braun, R.E. Development (2002) [Pubmed]
  27. Y-box binding protein 1: providing a new angle on translational regulation. Evdokimova, V., Ovchinnikov, L.P., Sorensen, P.H. Cell Cycle (2006) [Pubmed]
  28. Induction and suppression of glutathione transferases by interferon in the mouse. Adams, D.J., Balkwill, F.R., Griffin, D.B., Hayes, J.D., Lewis, A.D., Wolf, C.R. J. Biol. Chem. (1987) [Pubmed]
  29. Reprogramming of vascular smooth muscle alpha-actin gene expression as an early indicator of dysfunctional remodeling following heart transplant. Subramanian, S.V., Kelm, R.J., Polikandriotis, J.A., Orosz, C.G., Strauch, A.R. Cardiovasc. Res. (2002) [Pubmed]
  30. Regulation of YB-1 gene expression by GATA transcription factors. Yokoyama, H., Harigae, H., Takahashi, S., Takahashi, S., Furuyama, K., Kaku, M., Yamamoto, M., Sasaki, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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