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Gene Review

Pax5  -  paired box 5

Mus musculus

Synonyms: B-cell-specific transcription factor, BSAP, EBB-1, KLP, Paired box protein Pax-5, ...
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Disease relevance of Pax5


Psychiatry related information on Pax5

  • The only detectable effect of the Pax5 mutation was a delay in the development of the auditory sensitivity and response latency that correlates with the general growth retardation observed in these mice [6].

High impact information on Pax5


Chemical compound and disease context of Pax5

  • Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer [10].

Biological context of Pax5

  • Here we present a detailed analysis of the B-cell phenotype of Pax5 mutant mice that revealed a differential dependency of fetal and adult B lymphopoiesis on this transcriptional regulator [11].
  • Restoration of BLNK expression in Ig(mu) transgenic Pax5(-/-) pro-B cells resulted in constitutive pre-BCR signaling and increased cell proliferation without inducing progression to the pre-B cell stage [12].
  • In exploring the mechanism for Pax5 regulation of V(H)-to-DJ(H) recombination, we have identified multiple Pax5 binding sites in the coding regions of human and mouse V(H) gene segments [13].
  • The balance between Pax5 and Id2 activities is the key to AID gene expression [14].
  • The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as AID expression in primary B cells [14].

Anatomical context of Pax5

  • Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors [9].
  • The Pax5 gene coding for the transcription factor BSAP has an essential role in B lymphopoiesis and midbrain development [11].
  • However, Pax5-deficient fetal liver cells gave rise to the development of pre-BI cells in bone marrow on transplantation into lethally irradiated mice [11].
  • Pax5 thereby interfered with T lineage commitment and early thymocyte development by repressing the transcription of the T cell specification gene Notch1 [15].
  • Conditional and constitutive activation of the Ik(Pax5) allele demonstrated that precocious Pax5 expression in hematopoietic stem cells and progenitors failed to interfere with myeloid development and only weakly affected erythroblast formation [15].

Associations of Pax5 with chemical compounds


Physical interactions of Pax5

  • Together these data indicate that Pax2 and homeodomain proteins directly bind to and cooperatively regulate the mhb enhancer of Pax5 [21].
  • Blimp-1 binds a site on the Pax-5 promoter in vitro and in vivo and represses the Pax-5 promoter in a binding-site-dependent manner [22].
  • When Pax5 binding to the enhancer in B cells was blocked in vivo by transfection with a triple-helix-forming oligonucleotide an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased [23].
  • These studies suggest that different NF-kappaB complexes are able to interact with a sequence overlapping the Pax-5 site on the blk promoter and that the relative levels of "bound" factor influence levels of blk expression [24].
  • Gene transfer and gel-shift assays demonstrate that EBB-1 is identical to Pax-5 and binds to promoters of VpreB and lambda5 as well as the KI and KII sites [25].

Regulatory relationships of Pax5

  • Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1 [15].
  • To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the Pax2 locus [26].
  • Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene [27].
  • Reconstitution of Pax5 expression in Pax5-/- pro-B cells induced large-scale contraction and distal VH-DJH rearrangements of the IgH locus [27].
  • To study the effect of Pax5 on the development of other hematopoietic lineages, we generated a heterozygous knockin mouse carrying a Pax5 minigene under the control of the Ikaros locus [15].

Other interactions of Pax5

  • These data suggest a molecular basis for the hierarchical dependence of Pax5 function on EBF and E2A in B lymphocyte development [1].
  • Therefore, STAT5 functions at a distinct step in regulating distal V(H) recombination in relation to the transcription factor Pax5 and histone methyltransferase Ezh2 [28].
  • Phenotypic and expression studies show that Bcl11a functions upstream of the transcription factors Ebf1 and Pax5 in the B cell pathway [29].
  • In Pax2 mutant embryos, expression of the endogenous Pax5 gene was, however, delayed and severely reduced in lateral aspects of the neural plate which, on neural tube closure, becomes the dorsal mhb region [21].
  • The expression of Pax5 and Pax8 is either not initiated at the midbrain-hindbrain boundary or is later not maintained in other expression domains [30].

Analytical, diagnostic and therapeutic context of Pax5


  1. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Maier, H., Ostraat, R., Gao, H., Fields, S., Shinton, S.A., Medina, K.L., Ikawa, T., Murre, C., Singh, H., Hardy, R.R., Hagman, J. Nat. Immunol. (2004) [Pubmed]
  2. Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm. Steinbach, J.P., Kozmik, Z., Pfeffer, P., Aguzzi, A. Int. J. Cancer (2001) [Pubmed]
  3. Rapid in vivo analysis of mutant forms of the LAT adaptor using Pax5-Lat double-deficient pro-B cells. Ardouin, L., Rolink, A.G., Mura, A.M., Gommeaux, J., Melchers, F., Busslinger, M., Malissen, M., Malissen, B. Eur. J. Immunol. (2005) [Pubmed]
  4. Oscillation between B-lymphoid and myeloid lineages in Myc-induced hematopoietic tumors following spontaneous silencing/reactivation of the EBF/Pax5 pathway. Yu, D., Allman, D., Goldschmidt, M.H., Atchison, M.L., Monroe, J.G., Thomas-Tikhonenko, A. Blood (2003) [Pubmed]
  5. Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors. Horowitz, M.C., Xi, Y., Pflugh, D.L., Hesslein, D.G., Schatz, D.G., Lorenzo, J.A., Bothwell, A.L. J. Immunol. (2004) [Pubmed]
  6. Normal brainstem auditory evoked potentials in Pax5-deficient mice despite morphologic alterations in the auditory midbrain region. Reimer, K., Urbánek, P., Busslinger, M., Ehret, G. Audiology (1996) [Pubmed]
  7. Independent regulation of the two Pax5 alleles during B-cell development. Nutt, S.L., Vambrie, S., Steinlein, P., Kozmik, Z., Rolink, A., Weith, A., Busslinger, M. Nat. Genet. (1999) [Pubmed]
  8. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Klemsz, M.J., McKercher, S.R., Celada, A., Van Beveren, C., Maki, R.A. Cell (1990) [Pubmed]
  9. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Rolink, A.G., Nutt, S.L., Melchers, F., Busslinger, M. Nature (1999) [Pubmed]
  10. Identification of oligopeptides binding to peritoneal tumors of gastric cancer. Akita, N., Maruta, F., Seymour, L.W., Kerr, D.J., Parker, A.L., Asai, T., Oku, N., Nakayama, J., Miyagawa, S. Cancer Sci. (2006) [Pubmed]
  11. Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Nutt, S.L., Urbánek, P., Rolink, A., Busslinger, M. Genes Dev. (1997) [Pubmed]
  12. Control of pre-BCR signaling by Pax5-dependent activation of the BLNK gene. Schebesta, M., Pfeffer, P.L., Busslinger, M. Immunity (2002) [Pubmed]
  13. Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. Zhang, Z., Espinoza, C.R., Yu, Z., Stephan, R., He, T., Williams, G.S., Burrows, P.D., Hagman, J., Feeney, A.J., Cooper, M.D. Nat. Immunol. (2006) [Pubmed]
  14. The balance between Pax5 and Id2 activities is the key to AID gene expression. Gonda, H., Sugai, M., Nambu, Y., Katakai, T., Agata, Y., Mori, K.J., Yokota, Y., Shimizu, A. J. Exp. Med. (2003) [Pubmed]
  15. Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Souabni, A., Cobaleda, C., Schebesta, M., Busslinger, M. Immunity (2002) [Pubmed]
  16. EBF-regulating Pax5 transcription is enhanced by STAT5 in the early stage of B cells. Hirokawa, S., Sato, H., Kato, I., Kudo, A. Eur. J. Immunol. (2003) [Pubmed]
  17. B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Johnson, K., Pflugh, D.L., Yu, D., Hesslein, D.G., Lin, K.I., Bothwell, A.L., Thomas-Tikhonenko, A., Schatz, D.G., Calame, K. Nat. Immunol. (2004) [Pubmed]
  18. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the regulation of Pax5 in lipopolysaccharide-activated B cells. Yoo, B.S., Boverhof, D.R., Shnaider, D., Crawford, R.B., Zacharewski, T.R., Kaminski, N.E. Toxicol. Sci. (2004) [Pubmed]
  19. DNA methylation dominates transcriptional silencing of Pax5 in terminally differentiated B cell lines. Danbara, M., Kameyama, K., Higashihara, M., Takagaki, Y. Mol. Immunol. (2002) [Pubmed]
  20. Identification of Pax5 as a target of MTA1 in B-cell lymphomas. Balasenthil, S., Gururaj, A.E., Talukder, A.H., Bagheri-Yarmand, R., Arrington, T., Haas, B.J., Braisted, J.C., Kim, I., Lee, N.H., Kumar, R. Cancer Res. (2007) [Pubmed]
  21. Pax2 and homeodomain proteins cooperatively regulate a 435 bp enhancer of the mouse Pax5 gene at the midbrain-hindbrain boundary. Pfeffer, P.L., Bouchard, M., Busslinger, M. Development (2000) [Pubmed]
  22. Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells. Lin, K.I., Angelin-Duclos, C., Kuo, T.C., Calame, K. Mol. Cell. Biol. (2002) [Pubmed]
  23. Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. Neurath, M.F., Max, E.E., Strober, W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. The transcription factor NF-kappaB/p50 interacts with the blk gene during B cell activation. Zwollo, P., Rao, S., Wallin, J.J., Gackstetter, E.R., Koshland, M.E. J. Biol. Chem. (1998) [Pubmed]
  25. Pax-5 is identical to EBB-1/KLP and binds to the VpreB and lambda5 promoters as well as the KI and KII sites upstream of the Jkappa genes. Tian, J., Okabe, T., Miyazaki, T., Takeshita, S., Kudo, A. Eur. J. Immunol. (1997) [Pubmed]
  26. Functional equivalence of the transcription factors Pax2 and Pax5 in mouse development. Bouchard, M., Pfeffer, P., Busslinger, M. Development (2000) [Pubmed]
  27. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Fuxa, M., Skok, J., Souabni, A., Salvagiotto, G., Roldan, E., Busslinger, M. Genes Dev. (2004) [Pubmed]
  28. Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Bertolino, E., Reddy, K., Medina, K.L., Parganas, E., Ihle, J., Singh, H. Nat. Immunol. (2005) [Pubmed]
  29. Bcl11a is essential for normal lymphoid development. Liu, P., Keller, J.R., Ortiz, M., Tessarollo, L., Rachel, R.A., Nakamura, T., Jenkins, N.A., Copeland, N.G. Nat. Immunol. (2003) [Pubmed]
  30. Characterization of three novel members of the zebrafish Pax2/5/8 family: dependency of Pax5 and Pax8 expression on the Pax2.1 (noi) function. Pfeffer, P.L., Gerster, T., Lun, K., Brand, M., Busslinger, M. Development (1998) [Pubmed]
  31. Lineage-specific regulation of the murine RAG-2 promoter: GATA-3 in T cells and Pax-5 in B cells. Kishi, H., Wei, X.C., Jin, Z.X., Fujishiro, Y., Nagata, T., Matsuda, T., Muraguchi, A. Blood (2000) [Pubmed]
  32. Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: evidence from targeted mutations. Schwarz, M., Alvarez-Bolado, G., Urbánek, P., Busslinger, M., Gruss, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  33. Flt3 ligand induces the outgrowth of Mac-1+B220+ mouse bone marrow progenitor cells restricted to macrophage differentiation that coexpress early B cell-associated genes. Dannaeus, K., Johannisson, A., Nilsson, K., Jönsson, J.I. Exp. Hematol. (1999) [Pubmed]
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