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Gene Review

YBX1  -  Y box binding protein 1

Homo sapiens

Synonyms: BP-8, CBF-A, CCAAT-binding transcription factor I subunit A, CSDA2, CSDB, ...
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Disease relevance of YBX1


Psychiatry related information on YBX1

  • In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making [6].

High impact information on YBX1


Chemical compound and disease context of YBX1

  • CONCLUSIONS: We hypothesize that early in prostate cancer progression, increased expression of YB-1 may increase P-gp activity which may in turn lower androgen levels in the prostate tumor cells [9].
  • We found that trichostatin A upregulated CAR expression and that irinotecan caused increased nuclear localization of YB-1 in both glioblastoma cell lines [10].
  • We examined the effects of non-cytotoxic and cytotoxic doses of arsenic(III) and chromium(VI) on nuclear binding of the transcription factors AP-1, NF-kappaB, Sp1, and YB-1 in human MDA-MB-435 breast cancer and rat H4IIE hepatoma cells [11].
  • Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer [12].

Biological context of YBX1


Anatomical context of YBX1

  • We found that breast tumors which were both estrogen receptor-negative and lymph node positive were associated with high YB-1 expression (P=0.017) [16].
  • A full-length YB-1 protein expressed in human lung fibroblasts was primarily located in the nucleus with punctate staining in cytoplasmic regions [17].
  • Nuclear YB-1 expression had a significant correlation with P-glycoprotein and PgR expression, and also with CD68 grade, concerning accumulation of tumor associated macrophages [18].
  • Ectopic expression of YB-1 and Puralpha in glial cells synergistically stimulated viral promoter activity via the 23-bp sequence element [19].
  • A yeast interaction trap screen using LexA-YY1 as a bait and a HeLa cell cDNA-acid patch fusion library identified YB-1 as a YY1-interacting protein [20].

Associations of YBX1 with chemical compounds

  • In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity [14].
  • Tumor-associated p53 mutants however are attenuated for YB1 nuclear localization as are mutants mutated in the proline-rich domain of p53 [21].
  • RESULTS: YB-1 expression is markedly increased during benign to malignant transformation and further following androgen ablation [9].
  • The Y box-binding protein (YB-1) binds to DNA sequences, present in the control regions of many genes, that contain an inverted CCAAT box [22].
  • Electrophoretic mobility shift assays (EMSA) using various IgRE-derived oligonucleotide probes containing serial two-base mutations showed that YB-1 protein was preferentially bound to the pyrimidine-rich sequence within the IgRE [23].

Physical interactions of YBX1

  • Ankrd2 binding to the ubiquitous transcription factor YB-1 can be demonstrated both in vitro and in vivo; this is not very surprising, since a similar interaction was previously described for CARP [24].
  • Using a yeast one-hybrid screen, we found the transcription factor Y box binding protein 1 (YB-1) interacts with the 5-HTT VNTR [25].
  • Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted CCAAT box, is not only involved in the transcription of various genes, but also in cell proliferation and DNA repair [26].
  • An In vivo coimmunoprecipitation assay showed that IRP2 bound to YB-1 in the presence of iron and a proteasome inhibitor [27].
  • We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay [28].

Regulatory relationships of YBX1

  • The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor [1].
  • Taken together, our results demonstrate that YB-1 overexpression can induce EGF independence in HMECs via activation of the EGFR pathway [29].
  • In the present study, we report that overexpression of a transfected gene encoding YB-1 in human HeLa cervical carcinoma cells significantly represses the transactivation of a minimal AP-1 reporter construct in response to the tumour promoter PMA [30].
  • RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells [31].
  • Therefore, the increased binding activity seen in TGF-beta-stimulated nuclear extracts was due primarily to relocalization of YB-1 from the cytoplasm to the nuclear compartment [17].

Other interactions of YBX1

  • By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Pura alpha and YB-1, to JCV regulatory sequences [2].
  • Using immunochemical coprecipitation methods, we observed binding of YB-1 and PCNA in vivo [13].
  • Interferon-gamma interferes with transforming growth factor-beta signaling through direct interaction of YB-1 with Smad3 [32].
  • However, cell growth could be blocked with an ErbB kinase inhibitor, indicating that EGFR signaling plays a major role in YB-1-induced growth factor independence [29].
  • Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells [29].

Analytical, diagnostic and therapeutic context of YBX1


  1. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Bargou, R.C., Jürchott, K., Wagener, C., Bergmann, S., Metzner, S., Bommert, K., Mapara, M.Y., Winzer, K.J., Dietel, M., Dörken, B., Royer, H.D. Nat. Med. (1997) [Pubmed]
  2. Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element. Chen, N.N., Chang, C.F., Gallia, G.L., Kerr, D.A., Johnson, E.M., Krachmarov, C.P., Barr, S.M., Frisque, R.J., Bollag, B., Khalili, K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma. Oda, Y., Sakamoto, A., Shinohara, N., Ohga, T., Uchiumi, T., Kohno, K., Tsuneyoshi, M., Kuwano, M., Iwamoto, Y. Clin. Cancer Res. (1998) [Pubmed]
  4. Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma. Oda, Y., Ohishi, Y., Saito, T., Hinoshita, E., Uchiumi, T., Kinukawa, N., Iwamoto, Y., Kohno, K., Kuwano, M., Tsuneyoshi, M. J. Pathol. (2003) [Pubmed]
  5. Expression of Y box-binding protein-1 correlates with DNA topoisomerase IIalpha and proliferating cell nuclear antigen expression in lung cancer. Gu, C., Oyama, T., Osaki, T., Kohno, K., Yasumoto, K. Anticancer Res. (2001) [Pubmed]
  6. Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1. Janz, M., Harbeck, N., Dettmar, P., Berger, U., Schmidt, A., Jürchott, K., Schmitt, M., Royer, H.D. Int. J. Cancer (2002) [Pubmed]
  7. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Chen, C.Y., Gherzi, R., Andersen, J.S., Gaietta, G., Jürchott, K., Royer, H.D., Mann, M., Karin, M. Genes Dev. (2000) [Pubmed]
  8. Thrombin activates a Y box-binding protein (DNA-binding protein B) in endothelial cells. Stenina, O.I., Poptic, E.J., DiCorleto, P.E. J. Clin. Invest. (2000) [Pubmed]
  9. YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. Giménez-Bonafé, P., Fedoruk, M.N., Whitmore, T.G., Akbari, M., Ralph, J.L., Ettinger, S., Gleave, M.E., Nelson, C.C. Prostate (2004) [Pubmed]
  10. Novel three-pronged strategy to enhance cancer cell killing in glioblastoma cell lines: histone deacetylase inhibitor, chemotherapy, and oncolytic adenovirus dl520. Bieler, A., Mantwill, K., Dravits, T., Bernshausen, A., Glockzin, G., Köhler-Vargas, N., Lage, H., Gansbacher, B., Holm, P.S. Hum. Gene Ther. (2006) [Pubmed]
  11. Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Kaltreider, R.C., Pesce, C.A., Ihnat, M.A., Lariviere, J.P., Hamilton, J.W. Mol. Carcinog. (1999) [Pubmed]
  12. Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer. Yahata, H., Kobayashi, H., Kamura, T., Amada, S., Hirakawa, T., Kohno, K., Kuwano, M., Nakano, H. J. Cancer Res. Clin. Oncol. (2002) [Pubmed]
  13. Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen. Ise, T., Nagatani, G., Imamura, T., Kato, K., Takano, H., Nomoto, M., Izumi, H., Ohmori, H., Okamoto, T., Ohga, T., Uchiumi, T., Kuwano, M., Kohno, K. Cancer Res. (1999) [Pubmed]
  14. YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene. Stein, U., Bergmann, S., Scheffer, G.L., Scheper, R.J., Royer, H.D., Schlag, P.M., Walther, W. Oncogene (2005) [Pubmed]
  15. Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. Sutherland, B.W., Kucab, J., Wu, J., Lee, C., Cheang, M.C., Yorida, E., Turbin, D., Dedhar, S., Nelson, C., Pollak, M., Leighton Grimes, H., Miller, K., Badve, S., Huntsman, D., Blake-Gilks, C., Chen, M., Pallen, C.J., Dunn, S.E. Oncogene (2005) [Pubmed]
  16. Y-box binding protein, YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer. Huang, J., Tan, P.H., Li, K.B., Matsumoto, K., Tsujimoto, M., Bay, B.H. Int. J. Oncol. (2005) [Pubmed]
  17. A member of the Y-box protein family interacts with an upstream element in the alpha1(I) collagen gene. Sun, W., Hou, F., Panchenko, M.P., Smith, B.D. Matrix Biol. (2001) [Pubmed]
  18. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma. Saji, H., Toi, M., Saji, S., Koike, M., Kohno, K., Kuwano, M. Cancer Lett. (2003) [Pubmed]
  19. Reciprocal interaction between two cellular proteins, Puralpha and YB-1, modulates transcriptional activity of JCVCY in glial cells. Safak, M., Gallia, G.L., Khalili, K. Mol. Cell. Biol. (1999) [Pubmed]
  20. Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins. Li, W.W., Hsiung, Y., Wong, V., Galvin, K., Zhou, Y., Shi, Y., Lee, A.S. Mol. Cell. Biol. (1997) [Pubmed]
  21. Nuclear localization of Y-box factor YB1 requires wild-type p53. Zhang, Y.F., Homer, C., Edwards, S.J., Hananeia, L., Lasham, A., Royds, J., Sheard, P., Braithwaite, A.W. Oncogene (2003) [Pubmed]
  22. Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light. Ohga, T., Koike, K., Ono, M., Makino, Y., Itagaki, Y., Tanimoto, M., Kuwano, M., Kohno, K. Cancer Res. (1996) [Pubmed]
  23. Y-box-binding protein YB-1 mediates transcriptional repression of human alpha 2(I) collagen gene expression by interferon-gamma. Higashi, K., Inagaki, Y., Suzuki, N., Mitsui, S., Mauviel, A., Kaneko, H., Nakatsuka, I. J. Biol. Chem. (2003) [Pubmed]
  24. The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle. Kojic, S., Medeot, E., Guccione, E., Krmac, H., Zara, I., Martinelli, V., Valle, G., Faulkner, G. J. Mol. Biol. (2004) [Pubmed]
  25. YB-1 and CTCF differentially regulate the 5-HTT polymorphic intron 2 enhancer which predisposes to a variety of neurological disorders. Klenova, E., Scott, A.C., Roberts, J., Shamsuddin, S., Lovejoy, E.A., Bergmann, S., Bubb, V.J., Royer, H.D., Quinn, J.P. J. Neurosci. (2004) [Pubmed]
  26. Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer. Yoshimatsu, T., Uramoto, H., Oyama, T., Yashima, Y., Gu, C., Morita, M., Sugio, K., Kohno, K., Yasumoto, K. Anticancer Res. (2005) [Pubmed]
  27. Novel translational control through an iron-responsive element by interaction of multifunctional protein YB-1 and IRP2. Ashizuka, M., Fukuda, T., Nakamura, T., Shirasuna, K., Iwai, K., Izumi, H., Kohno, K., Kuwano, M., Uchiumi, T. Mol. Cell. Biol. (2002) [Pubmed]
  28. Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression. Okamoto, T., Izumi, H., Imamura, T., Takano, H., Ise, T., Uchiumi, T., Kuwano, M., Kohno, K. Oncogene (2000) [Pubmed]
  29. Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells. Berquin, I.M., Pang, B., Dziubinski, M.L., Scott, L.M., Chen, Y.Q., Nolan, G.P., Ethier, S.P. Oncogene (2005) [Pubmed]
  30. YB-1 represses AP1-dependent gene transactivation and interacts with an AP-1 DNA sequence. Samuel, S., Twizere, J.C., Bernstein, L.R. Biochem. J. (2005) [Pubmed]
  31. RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells. Rapp, T.B., Yang, L., Conrad, E.U., Mandahl, N., Chansky, H.A. J. Orthop. Res. (2002) [Pubmed]
  32. Interferon-gamma interferes with transforming growth factor-beta signaling through direct interaction of YB-1 with Smad3. Higashi, K., Inagaki, Y., Fujimori, K., Nakao, A., Kaneko, H., Nakatsuka, I. J. Biol. Chem. (2003) [Pubmed]
  33. Direct involvement of the Y-box binding protein YB-1 in genotoxic stress-induced activation of the human multidrug resistance 1 gene. Ohga, T., Uchiumi, T., Makino, Y., Koike, K., Wada, M., Kuwano, M., Kohno, K. J. Biol. Chem. (1998) [Pubmed]
  34. Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related ABC transporters. Stein, U., Jürchott, K., Walther, W., Bergmann, S., Schlag, P.M., Royer, H.D. J. Biol. Chem. (2001) [Pubmed]
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