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LGALS3  -  lectin, galactoside-binding, soluble, 3

Homo sapiens

Synonyms: 35 kDa lectin, CBP 35, CBP35, Carbohydrate-binding protein 35, GAL3, ...
 
 
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Disease relevance of LGALS3

 

High impact information on LGALS3

  • In previous studies, a lectin designated as carbohydrate-binding protein 35 (CBP35) has been isolated from cultured 3T3 fibroblasts [5].
  • In the present study, rabbit antibodies directed against CBP35 were used to analyze the subcellular distribution of CBP35 in 3T3 cells [5].
  • These results are consistent with the finding that among several subcellular fractions, CBP35 can be found by immunoblotting procedures in the nuclear pellet, the soluble fraction, and the plasma membrane fraction of the postnuclear supernatant [5].
  • Genome-wide association studies have also been undertaken, and the pro-inflammatory cytokine lymphotoxin-alpha (LTA), and its key ligand galectin-2 (LGALS2) have been identified as genes implicated in predisposition for heart attack [6].
  • DNA analysis of a human pituitary tumor, breast carcinoma cell lines, and thyroid carcinoma cell lines showed that in cells expressing Gal-3 protein, the LGALS3 gene was unmethylated, whereas in Gal-3 null cells, the promoter of the LGALS3 gene was methylated [7].
 

Chemical compound and disease context of LGALS3

 

Biological context of LGALS3

 

Anatomical context of LGALS3

  • Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1) [12].
  • An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors [1].
  • We examined the expression of LGALS3 by use of real-time quantitative reverse transcription-polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy [2].
  • A population (10/30) of the non-small-cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells [2].
  • Contrary to LGALS3, galig appears to be tightly regulated and principally activated in leukocytes from peripheral blood [13].
 

Associations of LGALS3 with chemical compounds

  • The primary structure of galectin-3, a approximately 30 kDa galactoside-binding protein (aka CBP-35, mL-34, hL-31, L-29, Mac-2, and epsilon BP), reveals two structural domains: an amino-terminal domain consists of a Pro-Gly-rich motif, and a globular carboxyl-terminal domain containing a carbohydrate-binding site [14].
  • CBP35 could also be detected using a novel photoreactive alpha-D-galactose probe designed for the specific detection of CBP [15].
  • The widely distributed hL-31 (CBP35, epsilon BP, mL-34, L-29, Mac-2) is a Ca(2+)-independent galactoside-binding lectin which functions as a receptor on mammalian cells for glycoproteins containing poly-N-acetyllactosamine side chains [16].
  • However, upon activation by FcepsilonRI cross-linkage, gal3(-/-) BMMC secreted a significantly lower amount of histamine as well as the cytokine IL-4, compared with gal3(+/+) BMMC [17].
  • The potential function of this lactose-mediated interaction is discussed with respect to data recently reported by others showing that CBP35 is involved in in vitro mRNA splicing and that lactose inhibits the processing of the pre-RNA substrate [18].
  • Removal of alpha2-6 sialic acids from ST6Gal-I expressors by neuraminidase treatment restores gal-3 binding [19].
  • We found that DX-52-1 and HUK-921 bind galectin-3 outside of its beta-galactoside-binding site [20].
  • Galectin 3 induces the production of mononuclear cell-recruiting chemokines uniquely from synovial fibroblasts, but not matched skin fibroblasts, via a PI 3-kinase signaling pathway [21].
 

Physical interactions of LGALS3

  • Since anti-CBP70 was immunologically cross-reactive to np56, it is concluded that the galectin GCA binds to np56 via similar mechanisms as reported previously for the interaction of CBP-35 (galectin-3) and CBP-70 [22].
 

Regulatory relationships of LGALS3

  • These findings suggest a pivotal role for P-GAL3 in promoting TRAIL sensitivity through activation of a nonclassic apoptotic pathway and identify P-GAL3 as a novel regulator of PTEN [23].
 

Other interactions of LGALS3

 

Analytical, diagnostic and therapeutic context of LGALS3

  • Fine-needle aspiration specimens were evaluated for the presence of galectin-3 (GAL-3), the most promising molecular marker of malignancy [24].
  • Immunoblotting experiments showed that CBP35 is present in the 40S heterogeneous nuclear RNP complex from HIV-1-infected Molt-3 cells [15].
  • The complete coding sequence of the rabbit galectin-3-encoding cDNA (LGALS3) has been cloned in a single step by using RT-PCR and specific human LGALS3 cDNA primers [27].
  • In addition to the plasma membrane, CBP35 could also be found intracellularly, as revealed by immunofluorescence studies of fixed and permeabilized 3T3 cells [5].
  • Digestion of recombinant CBP35 with collagenase D, followed by purification using saccharide-specific affinity chromatography yielded a M(r) approximately 16,000 polypeptide, corresponding to the COOH-terminal domain (residues 118-264) of the CBP35 polypeptide [11].

References

  1. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Prasad, M.L., Pellegata, N.S., Huang, Y., Nagaraja, H.N., de la Chapelle, A., Kloos, R.T. Mod. Pathol. (2005) [Pubmed]
  2. Increased expression of the LGALS3 (galectin 3) gene in human non-small-cell lung cancer. Yoshimura, A., Gemma, A., Hosoya, Y., Komaki, E., Hosomi, Y., Okano, T., Takenaka, K., Matuda, K., Seike, M., Uematsu, K., Hibino, S., Shibuya, M., Yamada, T., Hirohashi, S., Kudoh, S. Genes Chromosomes Cancer (2003) [Pubmed]
  3. Fine-scale SNP map of an 11-kb genomic region at 22q13.1 containing the galectin-1 gene. Iida, A., Ozaki, K., Tanaka, T., Nakamura, Y. J. Hum. Genet. (2005) [Pubmed]
  4. Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. Sapio, M.R., Guerra, A., Posca, D., Limone, P.P., Deandrea, M., Motta, M., Troncone, G., Caleo, A., Vallefuoco, P., Rossi, G., Fenzi, G., Vitale, M. Endocr. Relat. Cancer (2007) [Pubmed]
  5. Endogenous lectins from cultured cells: subcellular localization of carbohydrate-binding protein 35 in 3T3 fibroblasts. Moutsatsos, I.K., Davis, J.M., Wang, J.L. J. Cell Biol. (1986) [Pubmed]
  6. Genetic susceptibility to myocardial infarction and coronary artery disease. Topol, E.J., Smith, J., Plow, E.F., Wang, Q.K. Hum. Mol. Genet. (2006) [Pubmed]
  7. Effects of DNA methylation on galectin-3 expression in pituitary tumors. Ruebel, K.H., Jin, L., Qian, X., Scheithauer, B.W., Kovacs, K., Nakamura, N., Zhang, H., Raz, A., Lloyd, R.V. Cancer Res. (2005) [Pubmed]
  8. Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22. Raimond, J., Zimonjic, D.B., Mignon, C., Mattei, M., Popescu, N.C., Monsigny, M., Legrand, A. Mamm. Genome (1997) [Pubmed]
  9. UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells. Ocklenburg, F., Moharregh-Khiabani, D., Geffers, R., Janke, V., Pfoertner, S., Garritsen, H., Groebe, L., Klempnauer, J., Dittmar, K.E., Weiss, S., Buer, J., Probst-Kepper, M. Lab. Invest. (2006) [Pubmed]
  10. Analyses of Five gallinacin genes and the Salmonella enterica serovar Enteritidis response in poultry. Hasenstein, J.R., Zhang, G., Lamont, S.J. Infect. Immun. (2006) [Pubmed]
  11. Carbohydrate-binding protein 35. I. Properties of the recombinant polypeptide and the individuality of the domains. Agrwal, N., Sun, Q., Wang, S.Y., Wang, J.L. J. Biol. Chem. (1993) [Pubmed]
  12. Signatures of human regulatory T cells: an encounter with old friends and new players. Pfoertner, S., Jeron, A., Probst-Kepper, M., Guzman, C.A., Hansen, W., Westendorf, A.M., Toepfer, T., Schrader, A.J., Franzke, A., Buer, J., Geffers, R. Genome Biol. (2006) [Pubmed]
  13. Identification of an internal gene to the human Galectin-3 gene with two different overlapping reading frames that do not encode Galectin-3. Guittaut, M., Charpentier, S., Normand, T., Dubois, M., Raimond, J., Legrand, A. J. Biol. Chem. (2001) [Pubmed]
  14. Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Ochieng, J., Fridman, R., Nangia-Makker, P., Kleiner, D.E., Liotta, L.A., Stetler-Stevenson, W.G., Raz, A. Biochemistry (1994) [Pubmed]
  15. Expression of nuclear lectin carbohydrate-binding protein 35 in human immunodeficiency virus type 1-infected Molt-3 cells. Schröder, H.C., Ushijima, H., Theis, C., Sève, A.P., Hubert, J., Müller, W.E. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. (1995) [Pubmed]
  16. Regulation of the expression of galactoside-binding lectin during human monocytic differentiation. Nangia-Makker, P., Ochieng, J., Christman, J.K., Raz, A. Cancer Res. (1993) [Pubmed]
  17. Role of Galectin-3 in Mast Cell Functions: Galectin-3-Deficient Mast Cells Exhibit Impaired Mediator Release and Defective JNK Expression. Chen, H.Y., Sharma, B.B., Yu, L., Zuberi, R., Weng, I.C., Kawakami, Y., Kawakami, T., Hsu, D.K., Liu, F.T. J. Immunol. (2006) [Pubmed]
  18. Evidence for a lactose-mediated association between two nuclear carbohydrate-binding proteins. Sève, A.P., Felin, M., Doyennette-Moyne, M.A., Sahraoui, T., Aubery, M., Hubert, J. Glycobiology (1993) [Pubmed]
  19. Sialylation of beta1 integrins blocks cell adhesion to galectin-3 and protects cells against galectin-3-induced apoptosis. Zhuo, Y., Chammas, R., Bellis, S.L. J. Biol. Chem. (2008) [Pubmed]
  20. Analogs of tetrahydroisoquinoline natural products that inhibit cell migration and target galectin-3 outside of its carbohydrate-binding site. Kahsai, A.W., Cui, J., Kaniskan, H.U., Garner, P.P., Fenteany, G. J. Biol. Chem. (2008) [Pubmed]
  21. Galectin 3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathways. Filer, A., Bik, M., Parsonage, G.N., Fitton, J., Trebilcock, E., Howlett, K., Cook, M., Raza, K., Simmons, D.L., Thomas, A.M., Salmon, M., Scheel-Toellner, D., Lord, J.M., Rabinovich, G.A., Buckley, C.D. Arthritis Rheum. (2009) [Pubmed]
  22. Forssman disaccharide is the specific ligand of a galectin from the sponge Geodia cydonium but does not mediate its binding to nuclear protein np56. Hanisch, F.G., Baldus, S.E., Kümmel, T.A. Glycobiology (1996) [Pubmed]
  23. Phosphorylated galectin-3 mediates tumor necrosis factor-related apoptosis-inducing ligand signaling by regulating phosphatase and tensin homologue deleted on chromosome 10 in human breast carcinoma cells. Mazurek, N., Sun, Y.J., Liu, K.F., Gilcrease, M.Z., Schober, W., Nangia-Makker, P., Raz, A., Bresalier, R.S. J. Biol. Chem. (2007) [Pubmed]
  24. Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. Niedziela, M., Maceluch, J., Korman, E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  25. Diagnostic Usefulness of HBME1, Galectin-3, CK19, and CITED1 and Evaluation of Their Expression in Encapsulated Lesions With Questionable Features of Papillary Thyroid Carcinoma. Scognamiglio, T., Hyjek, E., Kao, J., Chen, Y.T. Am. J. Clin. Pathol. (2006) [Pubmed]
  26. The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Ramasamy, S., Duraisamy, S., Barbashov, S., Kawano, T., Kharbanda, S., Kufe, D. Mol. Cell (2007) [Pubmed]
  27. Cloning of the cDNA encoding rabbit galectin-3. Gaudin, J.C., Monsigny, M., Legrand, A. Gene (1995) [Pubmed]
 
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