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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Lotus


Psychiatry related information on Lotus


High impact information on Lotus

  • Cellular responses to invasion-stimulatory molecules such as scatter factor, chemokines, leptin, trefoil factors, and bile acids or inhibitory factors such as platelet activating factor and thrombin depend on activation of trimeric G proteins, phosphoinositide 3-kinase, and the Rac and Rho family of small GTPases [7].
  • Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice [8].
  • Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein [9].
  • The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1) [10].
  • Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor [10].

Chemical compound and disease context of Lotus


Biological context of Lotus

  • As EGF-R expression is itself strongly induced after mucosal damage, the trefoil/EGF-R relationship may be pivotal in the generation and maintenance of the mucosal repair phenotype [15].
  • The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation [15].
  • Binding sites were found to be relatively homogeneously distributed on the plasmalemma proper, except for Lotus tetragonolobus lectin and Con A, which frequently bound in patches [16].
  • Potential antitumor target genes upregulated by GATA-4 and -5, the trefoil factors, inhibinalpha, and disabled-2 (Dab2) are also silenced, in GI cancers, with associated methylation of the promoters [17].
  • Transfection experiments also indicated that substituting a thymidine for a cytosine at the N position in the ERRE of the native ERRalpha target promoter trefoil factor 1 (TFF1) considerably diminished the transcriptional response of the ERRalpha/PGC-1alpha complex [18].

Anatomical context of Lotus

  • Stimulation of restitution by the trefoil peptide HSP was enhanced in a cooperative fashion by the addition of mucin glycoproteins purified from the colon or small intestine of either rat or man, achieving up to a 15-fold enhancement in restitution [19].
  • The most up-regulated genes in BE compared with squamous epithelium were trefoil factors, annexin A10, and galectin-4 [20].
  • CONCLUSIONS: Trefoil peptides and mucin glycoproteins protect gastrointestinal mucosa from a variety of insults [21].
  • PSP contains two trefoil motifs, has several pharmacological actions on the gut, and has growth factor properties on epithelial cells in vitro [22].
  • The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor [23].

Associations of Lotus with chemical compounds

  • By analogy with epidermal growth factor and EGF-like repeats, the P-domain, or trefoil motif, is a characteristic shuffled module containing six invariant cysteine residues that forms the basic unit for a family of mucin-associated peptides [24].
  • Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein [21].
  • Similar effects were observed when rat intestinal trefoil factor or human spasmolysin, another human trefoil peptide, were added alone or in the presence of human mucin glycoproteins [21].
  • The N-terminal domain has a trefoil knot, in which AdoMet or AdoHcy is bound in a novel, bent conformation [25].
  • Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus [26].

Gene context of Lotus


Analytical, diagnostic and therapeutic context of Lotus

  • Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that although both Sp1 and Sp3 bind to the estrogen-responsive trefoil factor 1 promoter in MCF-7 cells, they do not occupy the same promoter [32].
  • In the present study, evidence has been obtained from electron microscopy for the formation of highly ordered and distinct lattices for two bivalent complex type oligosaccharides cross-linked with soybean lectin (Glycine max) and isolectin A from Lotus tetragonolobus, respectively [33].
  • Microarray analysis identified trefoil factor family 3 (TFF3) as a gene expressed in biliary epithelial cells (BECs), regulated by interleukin (IL)-6, and potentially involved in biliary pathophysiology [34].
  • Sequence analysis of interleukin-1beta indicates that three phenylalanine residues located at positions 42, 101, and 146 are well conserved, separated by approximately 50 residues in the primary sequence, located in similar positions in the pseudo-symmetric units of the trefoil, and are juxtaposed to one another in conformational space [35].
  • The fucose binding proteins (FBP) extracted from Lotus tetragonolobus seeds were isolated by affinity chromatography and compared with affinity purified commercial preparations for physical, antigenic, and biological properties [36].


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  2. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Argani, P., Rosty, C., Reiter, R.E., Wilentz, R.E., Murugesan, S.R., Leach, S.D., Ryu, B., Skinner, H.G., Goggins, M., Jaffee, E.M., Yeo, C.J., Cameron, J.L., Kern, S.E., Hruban, R.H. Cancer Res. (2001) [Pubmed]
  3. Chromatin modification of the trefoil factor 1 gene in human breast cancer cells by the Ras/mitogen-activated protein kinase pathway. Espino, P.S., Li, L., He, S., Yu, J., Davie, J.R. Cancer Res. (2006) [Pubmed]
  4. Metabolism of oral trefoil factor 2 (TFF2) and the effect of oral and parenteral TFF2 on gastric and duodenal ulcer healing in the rat. Poulsen, S.S., Thulesen, J., Christensen, L., Nexo, E., Thim, L. Gut (1999) [Pubmed]
  5. Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells. Rodrigues, S., Attoub, S., Nguyen, Q.D., Bruyneel, E., Rodrigue, C.M., Westley, B.R., May, F.E., Thim, L., Mareel, M., Emami, S., Gespach, C. Oncogene (2003) [Pubmed]
  6. The diurnal rhythm of the cytoprotective human trefoil protein TFF2 is reduced by factors associated with gastric mucosal damage: ageing, Helicobacter pylori infection, and sleep deprivation. Johns, C.E., Newton, J.L., Westley, B.R., May, F.E. Am. J. Gastroenterol. (2005) [Pubmed]
  7. Clinical, cellular, and molecular aspects of cancer invasion. Mareel, M., Leroy, A. Physiol. Rev. (2003) [Pubmed]
  8. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Tebbutt, N.C., Giraud, A.S., Inglese, M., Jenkins, B., Waring, P., Clay, F.J., Malki, S., Alderman, B.M., Grail, D., Hollande, F., Heath, J.K., Ernst, M. Nat. Med. (2002) [Pubmed]
  9. Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Lefebvre, O., Chenard, M.P., Masson, R., Linares, J., Dierich, A., LeMeur, M., Wendling, C., Tomasetto, C., Chambon, P., Rio, M.C. Science (1996) [Pubmed]
  10. Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor. Chutipongtanate, S., Nakagawa, Y., Sritippayawan, S., Pittayamateekul, J., Parichatikanond, P., Westley, B.R., May, F.E., Malasit, P., Thongboonkerd, V. J. Clin. Invest. (2005) [Pubmed]
  11. The binding of peroxidase-labelled lectins to human breast epithelium. III--Altered fucose-binding patterns of breast carcinomas and their significance. Walker, R.A. J. Pathol. (1984) [Pubmed]
  12. Use of capillary affinity electrophoresis for the determination of lectin-sugar interactions. Kuhn, R., Frei, R., Christen, M. Anal. Biochem. (1994) [Pubmed]
  13. Lectin histochemistry of ovarian mucinous cystadenomas. Teh, M., Lee, Y.S. Int. J. Gynecol. Pathol. (1991) [Pubmed]
  14. Ultrasonographic features of the fetal Turner syndrome. Brown, B.S., Thompson, D.L. Journal of the Canadian Association of Radiologists. (1984) [Pubmed]
  15. The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation. Taupin, D., Wu, D.C., Jeon, W.K., Devaney, K., Wang, T.C., Podolsky, D.K. J. Clin. Invest. (1999) [Pubmed]
  16. Differentiated microdomains on the luminal surface of capillary endothelium: distribution of lectin receptors. Simionescu, M., Simionescu, N., Palade, G.E. J. Cell Biol. (1982) [Pubmed]
  17. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Akiyama, Y., Watkins, N., Suzuki, H., Jair, K.W., van Engeland, M., Esteller, M., Sakai, H., Ren, C.Y., Yuasa, Y., Herman, J.G., Baylin, S.B. Mol. Cell. Biol. (2003) [Pubmed]
  18. A single nucleotide in an estrogen-related receptor alpha site can dictate mode of binding and peroxisome proliferator-activated receptor gamma coactivator 1alpha activation of target promoters. Barry, J.B., Laganière, J., Giguère, V. Mol. Endocrinol. (2006) [Pubmed]
  19. Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway. Dignass, A., Lynch-Devaney, K., Kindon, H., Thim, L., Podolsky, D.K. J. Clin. Invest. (1994) [Pubmed]
  20. A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia. van Baal, J.W., Milano, F., Rygiel, A.M., Bergman, J.J., Rosmolen, W.D., van Deventer, S.J., Wang, K.K., Peppelenbosch, M.P., Krishnadath, K.K. Gastroenterology (2005) [Pubmed]
  21. Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein. Kindon, H., Pothoulakis, C., Thim, L., Lynch-Devaney, K., Podolsky, D.K. Gastroenterology (1995) [Pubmed]
  22. Crystal structure of a disulfide-linked "trefoil" motif found in a large family of putative growth factors. De, A., Brown, D.G., Gorman, M.A., Carr, M., Sanderson, M.R., Freemont, P.S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  23. The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets. Kato, Y., Muto, T., Tomura, T., Tsumura, H., Watarai, H., Mikayama, T., Ishizaka, K., Kuroki, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  24. The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia? Hoffmann, W., Hauser, F. Trends Biochem. Sci. (1993) [Pubmed]
  25. Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition. Ahn, H.J., Kim, H.W., Yoon, H.J., Lee, B.I., Suh, S.W., Yang, J.K. EMBO J. (2003) [Pubmed]
  26. Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus. Elias, L., Van Epps, D.E. Blood (1984) [Pubmed]
  27. IL-4 and IL-13 up-regulate intestinal trefoil factor expression: requirement for STAT6 and de novo protein synthesis. Blanchard, C., Durual, S., Estienne, M., Bouzakri, K., Heim, M.H., Blin, N., Cuber, J.C. J. Immunol. (2004) [Pubmed]
  28. Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells. May, F.E., Westley, B.R. J. Pathol. (1997) [Pubmed]
  29. The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa. Ruchaud-Sparagano, M.H., Westley, B.R., May, F.E. Cell. Mol. Life Sci. (2004) [Pubmed]
  30. Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas. Gürbüz, Y., Klöppel, G. Virchows Arch. (2004) [Pubmed]
  31. Temporal expression of trefoil peptides in the TGF-alpha knockout mouse after gastric ulceration. Cook, G.A., Yeomans, N.D., Giraud, A.S. Am. J. Physiol. (1997) [Pubmed]
  32. Differential intranuclear organization of transcription factors Sp1 and Sp3. He, S., Sun, J.M., Li, L., Davie, J.R. Mol. Biol. Cell (2005) [Pubmed]
  33. Formation of highly ordered cross-linked lattices between asparagine-linked oligosaccharides and lectins observed by electron microscopy. Bhattacharyya, L., Khan, M.I., Fant, J., Brewer, C.F. J. Biol. Chem. (1989) [Pubmed]
  34. Regulation and function of trefoil factor family 3 expression in the biliary tree. Nozaki, I., Lunz, J.G., Specht, S., Park, J.I., Giraud, A.S., Murase, N., Demetris, A.J. Am. J. Pathol. (2004) [Pubmed]
  35. Three topologically equivalent core residues affect the transition state ensemble in a protein folding reaction. Heidary, D.K., Jennings, P.A. J. Mol. Biol. (2002) [Pubmed]
  36. Characterization of Lotus tetragonolobus fucolectin components for differences in hemagglutinating and macrophage activating activities. Leu, R.W., Herriott, M.J., Worley, D.S. Immunobiology (1985) [Pubmed]
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