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Pbp2  -  phosphatidylethanolamine binding protein 2

Mus musculus

Synonyms: 1700023A18Rik, AI326308, PEBP-2, Pebp-2, Pebp2, ...
 
 
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Disease relevance of Pbp2

 

High impact information on Pbp2

  • Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2 [4].
  • We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function [5].
  • AML1 is the human homolog of the recently cloned mouse gene pebp2 alpha B, homologous to the DNA binding alpha subunit of the polyoma enhancer factor pebp2 [6].
  • The major species of PEBP2 alpha mRNA was expressed in T-cell lines but not in B-cell lines tested [1].
  • Evidence indicated that PEBP2 functions as a transcriptional activator and is involved in regulation of T-cell-specific gene expression [1].
 

Chemical compound and disease context of Pbp2

 

Biological context of Pbp2

  • Protein homology modeling suggests that pebp-2 protein is, however, topologically similar to other pebps and composed of Greek key fold motifs, a dominant beta-sheet formed from five anti-parallel beta strands forming a shallow groove associated with a putative phosphatidylethanolamine binding site [8].
  • These data raise the possibility that pebp-2 is a novel participant in the MAP kinase signaling pathway, with a role in spermatogenesis or posttesticular sperm maturation [8].
  • Expression data show that pebp-2 is a testis-specific 21-kDa protein found within late meiotic and haploid germ cells in a stage-specific pattern that is temporally distinct from that of pebp-1 [8].
  • Each of the two human genes encoding the alpha and beta subunits of a heterodimeric transcription factor, PEBP2, has been found at the breakpoints of two characteristic chromosome translocations associated with acute myeloid leukemia, suggesting that they are candidate proto-oncogenes [9].
  • PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells [10].
 

Anatomical context of Pbp2

  • Further, pebp-2 colocalizes with members of the MAP kinase pathway in late spermatocytes and spermatids and on the midpiece of epididymal sperm [8].
  • Jurkat cell extract contained PEBP2 site-binding protein(s) that cross-reacted with antimouse alpha A1 antibodies [10].
  • Immunofluorescence labeling of NIH 3T3 cells transfected with PEBP2 alpha and -beta cDNAs revealed that the full-size alpha A1 and alpha B1 proteins, the products of two related but distinct genes, are located in the nucleus, while the beta subunit is localized to the cytoplasm [9].
  • PEBP2 alphaB1 and the beta subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal [11].
  • Lastly, the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes, along with the inability of OSF2 to be upregulated by retinoic acid, unlike the other PEBP2 alpha factors, suggest that OSF2 is a new member of this family of transcription factors [12].
 

Associations of Pbp2 with chemical compounds

 

Physical interactions of Pbp2

  • This showed that GRX may be involved in the redox regulation of the DNA-binding activity of PEBP2 as is the case with thioredoxin [3].
  • AML1 contains a region of sequence homology to the Drosophila runt gene and the mouse polyomavirus enhancer binding protein PEBP2 alpha gene [14].
  • The repression of replication mediated by c-jun appears to be mediated by factor(s) that bind to PEBP4/2 target sequences as oligomers bearing the PEBP2/4 target site were capable of restoring polyoma DNA replication when added to UV-treated or c-jun over-expressing cells [15].
 

Regulatory relationships of Pbp2

  • Ultraviolet irradiation and c-jun over-expression regulates replication of polyoma sequences in WOP cells through a PEBP2 binding site [15].
 

Other interactions of Pbp2

 

Analytical, diagnostic and therapeutic context of Pbp2

References

  1. PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., Ito, Y. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  2. Overexpression of AML1 renders a T hybridoma resistant to T cell receptor-mediated apoptosis. Fujii, M., Hayashi, K., Niki, M., Chiba, N., Meguro, K., Endo, K., Kameoka, J., Ito, S., Abe, K., Watanabe, T., Satake, M. Oncogene (1998) [Pubmed]
  3. Mouse glutaredoxin - cDNA cloning, high level expression in E. coli and its possible implication in redox regulation of the DNA binding activity in transcription factor PEBP2. Nakamura, T., Ohno, T., Hirota, K., Nishiyama, A., Nakamura, H., Wada, H., Yodoi, J. Free Radic. Res. (1999) [Pubmed]
  4. Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. Lauzurica, P., Zhong, X.P., Krangel, M.S., Roberts, J.L. J. Exp. Med. (1997) [Pubmed]
  5. A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. Yagi, R., Chen, L.F., Shigesada, K., Murakami, Y., Ito, Y. EMBO J. (1999) [Pubmed]
  6. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Nucifora, G., Begy, C.R., Erickson, P., Drabkin, H.A., Rowley, J.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Ogawa, E., Inuzuka, M., Maruyama, M., Satake, M., Naito-Fujimoto, M., Ito, Y., Shigesada, K. Virology (1993) [Pubmed]
  8. Identification of a novel testis-specific member of the phosphatidylethanolamine binding protein family, pebp-2. Hickox, D.M., Gibbs, G., Morrison, J.R., Sebire, K., Edgar, K., Keah, H.H., Alter, K., Loveland, K.L., Hearn, M.T., de Kretser, D.M., O'Bryan, M.K. Biol. Reprod. (2002) [Pubmed]
  9. Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF. Lu, J., Maruyama, M., Satake, M., Bae, S.C., Ogawa, E., Kagoshima, H., Shigesada, K., Ito, Y. Mol. Cell. Biol. (1995) [Pubmed]
  10. Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2. Takahashi, A., Satake, M., Yamaguchi-Iwai, Y., Bae, S.C., Lu, J., Maruyama, M., Zhang, Y.W., Oka, H., Arai, N., Arai, K. Blood (1995) [Pubmed]
  11. Intrinsic transcriptional activation-inhibition domains of the polyomavirus enhancer binding protein 2/core binding factor alpha subunit revealed in the presence of the beta subunit. Kanno, T., Kanno, Y., Chen, L.F., Ogawa, E., Kim, W.Y., Ito, Y. Mol. Cell. Biol. (1998) [Pubmed]
  12. A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element. Geoffroy, V., Ducy, P., Karsenty, G. J. Biol. Chem. (1995) [Pubmed]
  13. Redox regulation of the DNA binding activity in transcription factor PEBP2. The roles of two conserved cysteine residues. Akamatsu, Y., Ohno, T., Hirota, K., Kagoshima, H., Yodoi, J., Shigesada, K. J. Biol. Chem. (1997) [Pubmed]
  14. Molecular basis of the t(8;21) translocation in acute myeloid leukaemia. Ohki, M. Semin. Cancer Biol. (1993) [Pubmed]
  15. Ultraviolet irradiation and c-jun over-expression regulates replication of polyoma sequences in WOP cells through a PEBP2 binding site. Rutberg, S.E., Fuchs, S.Y., Ronai, Z. Biochim. Biophys. Acta (1995) [Pubmed]
  16. Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. Bae, S.C., Yamaguchi-Iwai, Y., Ogawa, E., Maruyama, M., Inuzuka, M., Kagoshima, H., Shigesada, K., Satake, M., Ito, Y. Oncogene (1993) [Pubmed]
  17. Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene. Ogihara, H., Kanno, T., Morii, E., Kim, D.K., Lee, Y.M., Sato, M., Kim, W.Y., Nomura, S., Ito, Y., Kitamura, Y. Oncogene (1999) [Pubmed]
  18. Study of osteoblast-specific expression of one mouse osteocalcin gene: characterization of the factor binding to OSE2. Ducy, P., Geoffroy, V., Karsenty, G. Connect. Tissue Res. (1996) [Pubmed]
  19. Functional dissection of the alpha and beta subunits of transcription factor PEBP2 and the redox susceptibility of its DNA binding activity. Kagoshima, H., Akamatsu, Y., Ito, Y., Shigesada, K. J. Biol. Chem. (1996) [Pubmed]
  20. The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures. Tanaka, Y., Watanabe, T., Chiba, N., Niki, M., Kuroiwa, Y., Nishihira, T., Satomi, S., Ito, Y., Satake, M. Oncogene (1997) [Pubmed]
 
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