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Fap  -  fibroblast activation protein

Mus musculus

Synonyms: Dipeptidyl peptidase FAP, FAPalpha, Fibroblast activation protein alpha, Gelatine degradation protease FAP, Integral membrane serine protease, ...
 
 
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Disease relevance of Fap

 

High impact information on Fap

 

Chemical compound and disease context of Fap

 

Biological context of Fap

  • In this study, we used PCR/restriction-fragment length polymorphism, identified in interspecific back-crosses between Mus musculus and Mus spretus, to map the Fap gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identified FAP gene locus on human chromosome 2q23 [10].
  • The Fap gene spans approximately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp [10].
  • As part of an effort to generate animal models of FAP expression in epithelial tumorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog [10].
  • Whilst DPP-IV is the most exhaustively studied peptidase in this class, relatively less is known about the inhibitor/substrate specificity of its close homolog seprase [1].
  • To study the expression of FAP during mouse embryogenesis, a second Fap-deficient mouse strain expressing beta-Galactosidase under the control of the Fap promoter was generated by homologous recombination (Fap-/- lacZ mice) [11].
 

Anatomical context of Fap

 

Associations of Fap with chemical compounds

  • Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease [10].
  • Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha) [1].
  • The FAP homologue in Xenopus laevis has been reported to be induced in the thyroid hormone-induced tail resorption program during tadpole metamorphosis supporting a role for FAP in tissue remodeling processes during embryonic development [11].
  • Prostaglandin E(2), the predominant eicosanoid product of the airway epithelium, is a potent inhibitor of mitogenesis, collagen synthesis, and mesenchymal cell chemotaxis and therefore can suppress inflammation and fibroblast activation [14].
  • Further investigation of the cellular and molecular mechanisms of inflammatory reaction, fibroblast activation and extracellular matrix deposition following dermal injury by bleomycin treatment will lead to the better understanding of the pathophysiology and the exploration of effective treatment against scleroderma [15].
 

Other interactions of Fap

 

Analytical, diagnostic and therapeutic context of Fap

References

  1. Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha). Gilmore, B.F., Lynas, J.F., Scott, C.J., McGoohan, C., Martin, L., Walker, B. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  2. FAPalpha, a surface peptidase expressed during wound healing, is a tumor suppressor. Ramirez-Montagut, T., Blachere, N.E., Sviderskaya, E.V., Bennett, D.C., Rettig, W.J., Garin-Chesa, P., Houghton, A.N. Oncogene (2004) [Pubmed]
  3. Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis. Schmitt, A., Jouault, H., Guichard, J., Wendling, F., Drouin, A., Cramer, E.M. Blood (2000) [Pubmed]
  4. Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Huang, Y., Wang, S., Kelly, T. Cancer Res. (2004) [Pubmed]
  5. Impact of interleukin-13 responsiveness on the synthetic and proliferative properties of Th1- and Th2-type pulmonary granuloma fibroblasts. Jakubzick, C., Choi, E.S., Kunkel, S.L., Joshi, B.H., Puri, R.K., Hogaboam, C.M. Am. J. Pathol. (2003) [Pubmed]
  6. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. Loeffler, M., Krüger, J.A., Niethammer, A.G., Reisfeld, R.A. J. Clin. Invest. (2006) [Pubmed]
  7. Targeted disruption of mouse fibroblast activation protein. Niedermeyer, J., Kriz, M., Hilberg, F., Garin-Chesa, P., Bamberger, U., Lenter, M.C., Park, J., Viertel, B., Püschner, H., Mauz, M., Rettig, W.J., Schnapp, A. Mol. Cell. Biol. (2000) [Pubmed]
  8. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Adams, S., Miller, G.T., Jesson, M.I., Watanabe, T., Jones, B., Wallner, B.P. Cancer Res. (2004) [Pubmed]
  9. Clinical implications of fibroblast activation protein in patients with colon cancer. Henry, L.R., Lee, H.O., Lee, J.S., Klein-Szanto, A., Watts, P., Ross, E.A., Chen, W.T., Cheng, J.D. Clin. Cancer Res. (2007) [Pubmed]
  10. Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease. Niedermeyer, J., Enenkel, B., Park, J.E., Lenter, M., Rettig, W.J., Damm, K., Schnapp, A. Eur. J. Biochem. (1998) [Pubmed]
  11. Expression of the fibroblast activation protein during mouse embryo development. Niedermeyer, J., Garin-Chesa, P., Kriz, M., Hilberg, F., Mueller, E., Bamberger, U., Rettig, W.J., Schnapp, A. Int. J. Dev. Biol. (2001) [Pubmed]
  12. Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Kelly, T. Drug Resist. Updat. (2005) [Pubmed]
  13. Production of a fibroblast-stimulating factor by Schistosoma mansoni antigen-reactive T cell clones. Lammie, P.J., Michael, A.I., Linette, G.P., Phillips, S.M. J. Immunol. (1986) [Pubmed]
  14. Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling. Holgate, S.T., Peters-Golden, M., Panettieri, R.A., Henderson, W.R. J. Allergy Clin. Immunol. (2003) [Pubmed]
  15. Cellular and molecular mechanisms of bleomycin-induced murine scleroderma: current update and future perspective. Yamamoto, T., Nishioka, K. Exp. Dermatol. (2005) [Pubmed]
  16. cDNA cloning and expression of secreted Xenopus laevis dipeptidyl aminopeptidase IV. Vlasak, R., Vilas, U., Strobl, B., Kreil, G. Eur. J. Biochem. (1997) [Pubmed]
  17. Role of parathyroid hormone-related protein in tubulointerstitial apoptosis and fibrosis after folic acid-induced nephrotoxicity. Ortega, A., Rámila, D., Ardura, J.A., Esteban, V., Ruiz-Ortega, M., Barat, A., Gazapo, R., Bosch, R.J., Esbrit, P. J. Am. Soc. Nephrol. (2006) [Pubmed]
  18. Generation of a FasL-based proapoptotic fusion protein devoid of systemic toxicity due to cell-surface antigen-restricted Activation. Samel, D., Muller, D., Gerspach, J., Assohou-Luty, C., Sass, G., Tiegs, G., Pfizenmaier, K., Wajant, H. J. Biol. Chem. (2003) [Pubmed]
  19. Tryptase 4, a new member of the chromosome 17 family of mouse serine proteases. Wong, G.W., Li, L., Madhusudhan, M.S., Krilis, S.A., Gurish, M.F., Rothenberg, M.E., Sali, A., Stevens, R.L. J. Biol. Chem. (2001) [Pubmed]
  20. Loss of tumor necrosis factor alpha potentiates transforming growth factor beta-mediated pathogenic tissue response during wound healing. Saika, S., Ikeda, K., Yamanaka, O., Flanders, K.C., Okada, Y., Miyamoto, T., Kitano, A., Ooshima, A., Nakajima, Y., Ohnishi, Y., Kao, W.W. Am. J. Pathol. (2006) [Pubmed]
  21. Mouse fibroblast activation protein: molecular cloning, alternative splicing and expression in the reactive stroma of epithelial cancers. Niedermeyer, J., Scanlan, M.J., Garin-Chesa, P., Daiber, C., Fiebig, H.H., Old, L.J., Rettig, W.J., Schnapp, A. Int. J. Cancer (1997) [Pubmed]
  22. Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth. Cheng, J.D., Valianou, M., Canutescu, A.A., Jaffe, E.K., Lee, H.O., Wang, H., Lai, J.H., Bachovchin, W.W., Weiner, L.M. Mol. Cancer Ther. (2005) [Pubmed]
  23. Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. Lee, J., Fassnacht, M., Nair, S., Boczkowski, D., Gilboa, E. Cancer Res. (2005) [Pubmed]
 
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