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Gene Review

Prep  -  prolyl endopeptidase

Mus musculus

Synonyms: AI047692, AI450383, D10Wsu136e, PE, PEP, ...
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Disease relevance of Prep

  • To study the function of these domains, we deleted different portions of the PE structural gene and expressed these constructs in E. coli using an inducible T7 promoter [1].
  • PERA/Ei (PE) mice are highly susceptible to tumor induction by polyoma virus, whereas C57BR/cdj (BR) mice are highly resistant [2].
  • A PE protein expressed by Mycobacterium avium is an effective T-cell immunogen [3].
  • Pre-eclampsia (PE) is the most severe pregnancy-related disease, leading to high maternal and fetal morbidity/mortality [4].
  • Mouse Neuro-2a neuroblastoma and rat C6 glioma cloned cells were screened for neuropeptide-metabolizing peptidases using a kininase bioassay combined with a time-course bradykinin-product analysis, and a fluorimetric assay for prolyl endopeptidase [5].

Psychiatry related information on Prep


High impact information on Prep

  • Inhibitors of prolyl oligopeptidase reverse the effects of all three drugs on sensory neuron growth cone area and collapse [8].
  • Moreover, the development of Dictyostelium is sensitive to lithium and to valproic acid, but resistance to both is conferred by deletion of the gene that codes for prolyl oligopeptidase, which also regulates inositol metabolism [8].
  • Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop [9].
  • We found a highly conserved Phox2b proximal enhancer that mediates rhombomere-restricted expression and contains separate Pbx-Hox (PH) and Prep/Meis (P/M) binding sites [10].
  • PE mice respond to viral infection with a type 2 (IL-10) and BR mice with a type 1 (IL-12) cytokine response, underlining the importance of a sustained T cell response for effective antitumor immunity [2].

Chemical compound and disease context of Prep


Biological context of Prep


Anatomical context of Prep

  • Representative aminopeptidases and prolyl endopeptidase from murine macrophages: comparative activity levels in resident and elicited cells [17].
  • cDNA cloning of mouse prolyl endopeptidase and its involvement in DNA synthesis by Swiss 3T3 cells [15].
  • Sperm Prep column washes were toxic to mouse gametes and embryos and human sperm and had gel formation with the Limulus Amoebocyte Lysate assay [18].
  • When broth cultures enter the post-exponential growth (PE) phase or experience amino acid limitation, L. pneumophila accumulates the stringent response signal (p)ppGpp and expresses traits likely to promote transmission to a new phagocyte [19].
  • When administered intraperitoneally to mice, Fmoc-alanyl-pyrrolidine-2-nitrile crosses the blood-brain barrier to inhibit brain prolyl oligopeptidase [6].

Associations of Prep with chemical compounds


Enzymatic interactions of Prep

  • The culture supernatant was concentrated using a stirred cell with a 50 kDa cut-off membrane at 40 degrees . Further purification was carried out using Prep cell [23].

Regulatory relationships of Prep


Other interactions of Prep


Analytical, diagnostic and therapeutic context of Prep


  1. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Hwang, J., Fitzgerald, D.J., Adhya, S., Pastan, I. Cell (1987) [Pubmed]
  2. Polyoma virus-like particles elicit polarized cytokine responses in APCs from tumor-susceptible and -resistant mice. Velupillai, P., Garcea, R.L., Benjamin, T.L. J. Immunol. (2006) [Pubmed]
  3. A PE protein expressed by Mycobacterium avium is an effective T-cell immunogen. Parra, M., Cadieux, N., Pickett, T., Dheenadhayalan, V., Brennan, M.J. Infect. Immun. (2006) [Pubmed]
  4. Introducing a mouse model for pre-eclampsia: adoptive transfer of activated Th1 cells leads to pre-eclampsia-like symptoms exclusively in pregnant mice. Zenclussen, A.C., Fest, S., Joachim, R., Klapp, B.F., Arck, P.C. Eur. J. Immunol. (2004) [Pubmed]
  5. Neuropeptide-metabolizing peptidases in neuro-2a neuroblastoma and C6 glioma cells. Del Bel, E.A., Gambarini, A.G., Martins, A.R. J. Neurochem. (1986) [Pubmed]
  6. Inhibition of prolyl oligopeptidase by Fmoc-aminoacylpyrrolidine-2-nitriles. Li, J., Wilk, E., Wilk, S. J. Neurochem. (1996) [Pubmed]
  7. Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation. Laitinen, K.S., van Groen, T., Tanila, H., Venäläinen, J., Männistö, P.T., Alafuzoff, I. Neuroreport (2001) [Pubmed]
  8. A common mechanism of action for three mood-stabilizing drugs. Williams, R.S., Cheng, L., Mudge, A.W., Harwood, A.J. Nature (2002) [Pubmed]
  9. Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1. Zubair, M., Ishihara, S., Oka, S., Okumura, K., Morohashi, K. Mol. Cell. Biol. (2006) [Pubmed]
  10. Integration of anteroposterior and dorsoventral regulation of Phox2b transcription in cranial motoneuron progenitors by homeodomain proteins. Samad, O.A., Geisen, M.J., Caronia, G., Varlet, I., Zappavigna, V., Ericson, J., Goridis, C., Rijli, F.M. Development (2004) [Pubmed]
  11. Localization of endoderm-specific mRNAs in differentiating F9 embryoid bodies. Becker, S., Casanova, J., Grabel, L. Mech. Dev. (1992) [Pubmed]
  12. Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534-30F3. I. Taxonomy, production, isolation, physico-chemical properties and biological activities. Aoyagi, T., Nagai, M., Ogawa, K., Kojima, F., Okada, M., Ikeda, T., Hamada, M., Takeuchi, T. J. Antibiot. (1991) [Pubmed]
  13. Structure and localization of the mouse prolyl oligopeptidase gene. Kimura, A., Yoshida, I., Takagi, N., Takahashi, T. J. Biol. Chem. (1999) [Pubmed]
  14. Murine T cells expressing high activity of prolyl endopeptidase are susceptible to activation-induced cell death. Odaka, C., Mizuochi, T., Shirasawa, T., Morain, P., Checler, F. FEBS Lett. (2002) [Pubmed]
  15. cDNA cloning of mouse prolyl endopeptidase and its involvement in DNA synthesis by Swiss 3T3 cells. Ishino, T., Ohtsuki, S., Homma, K., Natori, S. J. Biochem. (1998) [Pubmed]
  16. The protein kinase C pathway acts through multiple transcription factors to repress gonadotropin-releasing hormone gene expression in hypothalamic GT1-7 neuronal cells. Tang, Q., Mazur, M., Mellon, P.L. Mol. Endocrinol. (2005) [Pubmed]
  17. Representative aminopeptidases and prolyl endopeptidase from murine macrophages: comparative activity levels in resident and elicited cells. Olivo, R.d.o. .A., Teixeira, C.d.e. .F., Silveira, P.F. Biochem. Pharmacol. (2005) [Pubmed]
  18. Mouse in vitro fertilization, embryo development and viability, and human sperm motility in substances used for human sperm preparation for assisted reproduction. Scott, L., Smith, S. Fertil. Steril. (1997) [Pubmed]
  19. RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase. Bachman, M.A., Swanson, M.S. Mol. Microbiol. (2001) [Pubmed]
  20. Regulation of prolyl endopeptidase activity by the intracellular redox state. Tsukahara, T., Ishiura, S., Sugita, H. J. Biol. Chem. (1990) [Pubmed]
  21. Prolyl endopeptidase: inhibition in vivo by N-benzyloxycarbonyl-prolyl-prolinal. Friedman, T.C., Orlowski, M., Wilk, S. J. Neurochem. (1984) [Pubmed]
  22. Engineering a thermostable human prolyl endopeptidase for antibody-directed enzyme prodrug therapy. Heinis, C., Alessi, P., Neri, D. Biochemistry (2004) [Pubmed]
  23. Development of an immunodetection test for a botulinum - like neurotoxin produced by Clostridium sp. RKD. Dixit, A., Alam, S.I., Dhaked, R.K., Singh, L. Indian J. Med. Res. (2006) [Pubmed]
  24. Specific inhibitor for prolyl endopeptidase suppresses the generation of amyloid beta protein in NG108-15 cells. Shinoda, M., Toide, K., Ohsawa, I., Kohsaka, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  25. Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV activities in the mouse uterus and ovary. Ohta, N., Takahashi, T., Mori, T., Park, M.K., Kawashima, S., Takahashi, K., Kobayashi, H. Acta Endocrinol. (1992) [Pubmed]
  26. Proteases in the Emory mouse cataract. Swanson, A.A., Davis, R.M., Meinhardt, N.C., Kuck, K.D., Kuck, J.F. Invest. Ophthalmol. Vis. Sci. (1985) [Pubmed]
  27. Prevention of amyloid-like deposition by a selective prolyl endopeptidase inhibitor, Y-29794, in senescence-accelerated mouse. Kato, A., Fukunari, A., Sakai, Y., Nakajima, T. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  28. Specific inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase do not change the in vitro release of TRH or its content in rodent brain. Charli, J.L., Mendez, M., Joseph-Bravo, P., Wilk, S. Neuropeptides (1987) [Pubmed]
  29. Three modes of age-related changes of hydrolytic enzymes in murine brain. Aoyagi, T., Wada, T., Kojima, F., Nagai, M., Osanai, M., Imahori, K., Umezawa, H. Biotechnol. Appl. Biochem. (1986) [Pubmed]
  30. Purification and characterization of prolyl endopeptidase from the Pacific herring, Clupea pallasi, and its role in the activation of sperm motility. Yoshida, K., Inaba, K., Ohtake, H., Morisawa, M. Dev. Growth Differ. (1999) [Pubmed]
  31. Preparative in situ hybridization: selection of chromosome region-specific libraries on mitotic chromosomes. Hozier, J., Graham, R., Westfall, T., Siebert, P., Davis, L. Genomics (1994) [Pubmed]
  32. Protease inhibition increases the analgesic potency of peptide E. Westphal, M., Hammonds, R.G., Li, C.H. Neuropharmacology (1985) [Pubmed]
  33. A comparative analysis of the antigenic, structural, and functional properties of three different preparations of recombinant human interleukin-18. Kikkawa, S., Shida, K., Okamura, H., Begum, N.A., Matsumoto, M., Tsuji, S., Nomura, M., Suzuki, Y., Toyoshima, K., Seya, T. J. Interferon Cytokine Res. (2000) [Pubmed]
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