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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Ligation

  • RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation [1].
  • In the smaller infants indomethacin therapy was associated with a significantly lower incidence of major shunts, fewer surgical ligations, a decreased duration of oxygen therapy, and fewer days necessary to regain birth weight [2].
  • As HIV-1 also enhances Fas expression on virally infected cells, it is unclear how these hosts avoid rapid cell-autonomous apoptosis mediated through cis ligation of Fas by FasL [3].
  • Bis-methionine axial ligation of haem in bacterioferritin from Pseudomonas aeruginosa [4].
  • Here, we report that transfer of the gene encoding second mitochondria-derived activator of caspase (Smac) or Smac peptides sensitized various tumor cells in vitro and malignant glioma cells in vivo for apoptosis induced by death-receptor ligation or cytotoxic drugs [5].

High impact information on Ligation

  • Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial [6].
  • T lymphocytes also require activation of tyrosine kinases following T cell receptor (TCR) ligation for maximal stimulation [7].
  • CD2 ligation can mediate or enhance T-cell activation, suggesting that signals from CD2/LFA-3 adhesive interactions are integrated with signals from the T-cell antigen receptor during immunological recognition [8].
  • The RNA terminated region is displaced into a 5' single-stranded flap, which is removed by the structure-specific flap endonuclease 1 (FEN1), leaving a nick for ligation [9].
  • This review summarizes current efforts to obtain homogeneous glycopeptide and glycoprotein materials by a variety of methods that draw from the techniques of recombinant expression, chemical synthesis, enzymatic transformation, and chemoselective ligation [10].

Chemical compound and disease context of Ligation


Biological context of Ligation

  • Intracellular signal transduction following the extracellular ligation of a wide variety of different types of surface molecules on leukocytes involves the activation of protein tyrosine kinases [16].
  • Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation [17].
  • The reactions that were characterized included the precise excision of the IVS, attachment of guanosine to the 5' end of the IVS, covalent cyclization of the IVS and ligation of the exons [18].
  • Mutagenesis and dominant-negative inhibition studies reveal that Shc is necessary and sufficient for activation of the MAP kinase pathway in response to integrin ligation [19].
  • A detailed examination of the Drosophila Sex-lethal gene has led to two significant discoveries-the role of the splicing factor SPF45 in defining the site of exon ligation, and that alternative splicing can be regulated at the second step [20].

Anatomical context of Ligation

  • We demonstrate therefore that ligation of integrin alpha v beta 3 is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors [21].
  • Excision of introns from nuclear precursors to messenger RNAs (pre-mRNAs) by the spliceosome requires two distinct phosphodiester transfer (transesterification) reactions: exchange of a 3'-5' for a 2'-5' bond in the first step (lariat formation) and exchange of one 3'-5' phosphodiester for another in the second step (exon ligation) [22].
  • In B-cell lines derived from c-rel-/- mice, which like primary cells lacking Rel undergo apoptosis in response to antigen receptor ligation, constitutive expression of an A1 transgene inhibits this pathway to cell death [23].
  • More dramatically, SLP-76-/- neutrophils fail to produce ROI, spread, or activate critical downstream regulators in response to integrin ligation [24].
  • We show here that treatment of infected macrophages with ATP leads to killing of chlamydiae through ligation of the purinergic receptor, P2X(7)R [25].

Associations of Ligation with chemical compounds


Gene context of Ligation

  • Arthrin reacts with an anti-ubiquitin antibody, which demonstrates that its extra mass results from ubiquitin ligation [30].
  • Upon exon ligation, association of RNPS1, UAP56, and SRm160 is destabilized [31].
  • Here, we demonstrate that beta1 integrin ligation on human NK cells results in the activation of the p38 MAPK signaling pathway, which is required for integrin-triggered IL-8 production [32].
  • A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo [33].
  • These differences suggest that another adapter must exist that can mediate MyD88-independent signaling in response to TLR4 ligation [34].

Analytical, diagnostic and therapeutic context of Ligation


  1. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. Sarin, S.K., Lamba, G.S., Kumar, M., Misra, A., Murthy, N.S. N. Engl. J. Med. (1999) [Pubmed]
  2. Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants. Mahony, L., Carnero, V., Brett, C., Heymann, M.A., Clyman, R.I. N. Engl. J. Med. (1982) [Pubmed]
  3. HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Geleziunas, R., Xu, W., Takeda, K., Ichijo, H., Greene, W.C. Nature (2001) [Pubmed]
  4. Bis-methionine axial ligation of haem in bacterioferritin from Pseudomonas aeruginosa. Cheesman, M.R., Thomson, A.J., Greenwood, C., Moore, G.R., Kadir, F. Nature (1990) [Pubmed]
  5. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Fulda, S., Wick, W., Weller, M., Debatin, K.M. Nat. Med. (2002) [Pubmed]
  6. Origins and functions of B-1 cells with notes on the role of CD5. Berland, R., Wortis, H.H. Annu. Rev. Immunol. (2002) [Pubmed]
  7. Integration of T cell receptor-dependent signaling pathways by adapter proteins. Clements, J.L., Boerth, N.J., Lee, J.R., Koretzky, G.A. Annu. Rev. Immunol. (1999) [Pubmed]
  8. Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Dustin, M.L., Springer, T.A. Annu. Rev. Immunol. (1991) [Pubmed]
  9. Flap endonuclease 1: a central component of DNA metabolism. Liu, Y., Kao, H.I., Bambara, R.A. Annu. Rev. Biochem. (2004) [Pubmed]
  10. Homogeneous glycopeptides and glycoproteins for biological investigation. Grogan, M.J., Pratt, M.R., Marcaurelle, L.A., Bertozzi, C.R. Annu. Rev. Biochem. (2002) [Pubmed]
  11. The hepatitis C envelope 2 protein inhibits LFA-1-transduced protein kinase C signaling for T-lymphocyte migration. Volkov, Y., Long, A., Freeley, M., Golden-Mason, L., O'Farrelly, C., Murphy, A., Kelleher, D. Gastroenterology (2006) [Pubmed]
  12. Diadenosine tetraphosphate as a signal molecule linked with the functional state of rat liver. Yamaguchi, N., Kodama, M., Ueda, K. Gastroenterology (1985) [Pubmed]
  13. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Jonsson, J.R., Clouston, A.D., Ando, Y., Kelemen, L.I., Horn, M.J., Adamson, M.D., Purdie, D.M., Powell, E.E. Gastroenterology (2001) [Pubmed]
  14. Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation. Sung, J.J., Chung, S.C., Yung, M.Y., Lai, C.W., Lau, J.Y., Lee, Y.T., Leung, V.K., Li, M.K., Li, A.K. Lancet (1995) [Pubmed]
  15. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Anand, K.J., Sippell, W.G., Aynsley-Green, A. Lancet (1987) [Pubmed]
  16. Leukocyte protein tyrosine kinases: potential targets for drug discovery. Bolen, J.B., Brugge, J.S. Annu. Rev. Immunol. (1997) [Pubmed]
  17. In vitro selection of functional nucleic acids. Wilson, D.S., Szostak, J.W. Annu. Rev. Biochem. (1999) [Pubmed]
  18. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E., Cech, T.R. Cell (1982) [Pubmed]
  19. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Wary, K.K., Mainiero, F., Isakoff, S.J., Marcantonio, E.E., Giancotti, F.G. Cell (1996) [Pubmed]
  20. Sex, AGility, and the regulation of alternative splicing. Graveley, B.R. Cell (2002) [Pubmed]
  21. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Brooks, P.C., Montgomery, A.M., Rosenfeld, M., Reisfeld, R.A., Hu, T., Klier, G., Cheresh, D.A. Cell (1994) [Pubmed]
  22. Evidence for two active sites in the spliceosome provided by stereochemistry of pre-mRNA splicing. Moore, M.J., Sharp, P.A. Nature (1993) [Pubmed]
  23. Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. Grumont, R.J., Rourke, I.J., Gerondakis, S. Genes Dev. (1999) [Pubmed]
  24. SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils. Newbrough, S.A., Mocsai, A., Clemens, R.A., Wu, J.N., Silverman, M.A., Singer, A.L., Lowell, C.A., Koretzky, G.A. Immunity (2003) [Pubmed]
  25. Inhibition of chlamydial infectious activity due to P2X7R-dependent phospholipase D activation. Coutinho-Silva, R., Stahl, L., Raymond, M.N., Jungas, T., Verbeke, P., Burnstock, G., Darville, T., Ojcius, D.M. Immunity (2003) [Pubmed]
  26. Structure-based perspectives on B12-dependent enzymes. Ludwig, M.L., Matthews, R.G. Annu. Rev. Biochem. (1997) [Pubmed]
  27. Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding. Villanueva, C., Miñana, J., Ortiz, J., Gallego, A., Soriano, G., Torras, X., Sáinz, S., Boadas, J., Cussó, X., Guarner, C., Balanzó, J. N. Engl. J. Med. (2001) [Pubmed]
  28. Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome. Green, T.P., Thompson, T.R., Johnson, D.E., Lock, J.E. N. Engl. J. Med. (1983) [Pubmed]
  29. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. van der Veen, R., Arnberg, A.C., van der Horst, G., Bonen, L., Tabak, H.F., Grivell, L.A. Cell (1986) [Pubmed]
  30. Arthrin, a myofibrillar protein of insect flight muscle, is an actin-ubiquitin conjugate. Ball, E., Karlik, C.C., Beall, C.J., Saville, D.L., Sparrow, J.C., Bullard, B., Fyrberg, E.A. Cell (1987) [Pubmed]
  31. 5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly. Reichert, V.L., Le Hir, H., Jurica, M.S., Moore, M.J. Genes Dev. (2002) [Pubmed]
  32. RAC1/P38 MAPK signaling pathway controls beta1 integrin-induced interleukin-8 production in human natural killer cells. Mainiero, F., Soriani, A., Strippoli, R., Jacobelli, J., Gismondi, A., Piccoli, M., Frati, L., Santoni, A. Immunity (2000) [Pubmed]
  33. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Hodge, M.R., Ranger, A.M., Charles de la Brousse, F., Hoey, T., Grusby, M.J., Glimcher, L.H. Immunity (1996) [Pubmed]
  34. TIRAP: an adapter molecule in the Toll signaling pathway. Horng, T., Barton, G.M., Medzhitov, R. Nat. Immunol. (2001) [Pubmed]
  35. A CD14-independent LPS receptor cluster. Triantafilou, K., Triantafilou, M., Dedrick, R.L. Nat. Immunol. (2001) [Pubmed]
  36. Residual type 1 immunity in patients genetically deficient for interleukin 12 receptor beta1 (IL-12Rbeta1): evidence for an IL-12Rbeta1-independent pathway of IL-12 responsiveness in human T cells. Verhagen, C.E., de Boer T, n.u.l.l., Smits, H.H., Verreck, F.A., Wierenga, E.A., Kurimoto, M., Lammas, D.A., Kumararatne, D.S., Sanal, O., Kroon, F.P., van Dissel JT, n.u.l.l., Sinigaglia, F., Ottenhoff, T.H. J. Exp. Med. (2000) [Pubmed]
  37. Ligation of CD38 suppresses human B lymphopoiesis. Kumagai, M., Coustan-Smith, E., Murray, D.J., Silvennoinen, O., Murti, K.G., Evans, W.E., Malavasi, F., Campana, D. J. Exp. Med. (1995) [Pubmed]
  38. Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion. Becker, L.C. J. Clin. Invest. (1976) [Pubmed]
  39. Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism. Wong, K.K., Carpenter, M.J., Young, L.L., Walker, S.J., McKenzie, G., Rust, A.J., Ward, G., Packwood, L., Wahl, K., Delriviere, L., Hoyne, G., Gibbs, P., Champion, B.R., Lamb, J.R., Dallman, M.J. J. Clin. Invest. (2003) [Pubmed]
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