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Proc Natl Acad Sci U S A. Jun 25, 1996; 93(13): 6737–6742.

Expression of galectin-3 modulates T-cell growth and apoptosis.


Galectin-3 is a member (if a large family of beta-galactoside-binding animal lectins. It has been shown that the expression of galectin-3 is upregulated in proliferating cells, suggesting a possible role for this lectin in regulation of cell growth. Previously, we have shown that T cells infected with human T-cell leukemia virus type I express high levels of galectin-3, in contrast to uninfected cells, which do not express detectable amounts of this protein. In this study, we examined growth properties of human leukemia T cells transfected with galectin-3 cDNA, and thus constitutively overexpressing this lectin. Transfectants expressing galectin-3 displayed higher growth rates than control transfectants, which do not express this lectin. Furthermore, galectin-3 expression in these cells confers resistance to apoptosis induced by anti-Fas antibody and staurosporine. Galectin-3 was found to have significant sequence similarity with Bcl-2, a well-characterized suppressor of apoptosis. In particular, the lectin contains the NWGR motif that is highly conserved among members of the Bcl-2 family and shown to be critical for the apoptosis-suppressing activity. We further demonstrated that galectin-3 interacts with Bc1-2 in a lactose-inhibitable manner. We conclude that galectin-3 is a regulator of cell growth and apoptosis and it may function through a cell death inhibition pathway that involves Bcl-2.

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  • Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995 Mar 10;267(5203):1456–1462. [PubMed]
  • Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, Gitt MA, Hirabayashi J, Hughes C, Kasai K, et al. Galectins: a family of animal beta-galactoside-binding lectins. Cell. 1994 Feb 25;76(4):597–598. [PubMed]
  • Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994 Aug 19;269(33):20807–20810. [PubMed]
  • Liu FT. Molecular biology of IgE-binding protein, IgE-binding factors, and IgE receptors. Crit Rev Immunol. 1990;10(3):289–306. [PubMed]
  • Crittenden SL, Roff CF, Wang JL. Carbohydrate-binding protein 35: identification of the galactose-specific lectin in various tissues of mice. Mol Cell Biol. 1984 Jul;4(7):1252–1259. [PMC free article] [PubMed]
  • Flotte TJ, Springer TA, Thorbecke GJ. Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets. Am J Pathol. 1983 Apr;111(1):112–124. [PMC free article] [PubMed]
  • Gritzmacher CA, Robertson MW, Liu FT. IgE-binding protein. Subcellular location and gene expression in many murine tissues and cells. J Immunol. 1988 Oct 15;141(8):2801–2806. [PubMed]
  • Moutsatsos IK, Wade M, Schindler M, Wang JL. Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6452–6456. [PMC free article] [PubMed]
  • Frigeri LG, Liu FT. Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages. J Immunol. 1992 Feb 1;148(3):861–867. [PubMed]
  • Sato S, Hughes RC. Regulation of secretion and surface expression of Mac-2, a galactoside-binding protein of macrophages. J Biol Chem. 1994 Feb 11;269(6):4424–4430. [PubMed]
  • Sato S, Burdett I, Hughes RC. Secretion of the baby hamster kidney 30-kDa galactose-binding lectin from polarized and nonpolarized cells: a pathway independent of the endoplasmic reticulum-Golgi complex. Exp Cell Res. 1993 Jul;207(1):8–18. [PubMed]
  • Lindstedt R, Apodaca G, Barondes SH, Mostov KE, Leffler H. Apical secretion of a cytosolic protein by Madin-Darby canine kidney cells. Evidence for polarized release of an endogenous lectin by a nonclassical secretory pathway. J Biol Chem. 1993 Jun 5;268(16):11750–11757. [PubMed]
  • Dagher SF, Wang JL, Patterson RJ. Identification of galectin-3 as a factor in pre-mRNA splicing. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1213–1217. [PMC free article] [PubMed]
  • Raz A, Zhu DG, Hogan V, Shah N, Raz T, Karkash R, Pazerini G, Carmi P. Evidence for the role of 34-kDa galactoside-binding lectin in transformation and metastasis. Int J Cancer. 1990 Nov 15;46(5):871–877. [PubMed]
  • Liu FT. S-type mammalian lectins in allergic inflammation. Immunol Today. 1993 Oct;14(10):486–490. [PubMed]
  • Agrwal N, Wang JL, Voss PG. Carbohydrate-binding protein 35. Levels of transcription and mRNA accumulation in quiescent and proliferating cells. J Biol Chem. 1989 Oct 15;264(29):17236–17242. [PubMed]
  • Cowles EA, Agrwal N, Anderson RL, Wang JL. Carbohydrate-binding protein 35. Isoelectric points of the polypeptide and a phosphorylated derivative. J Biol Chem. 1990 Oct 15;265(29):17706–17712. [PubMed]
  • Hsu DK, Hammes SR, Kuwabara I, Greene WC, Liu FT. Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3. Am J Pathol. 1996 May;148(5):1661–1670. [PMC free article] [PubMed]
  • Krajewski S, Krajewska M, Shabaik A, Wang HG, Irie S, Fong L, Reed JC. Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res. 1994 Nov 1;54(21):5501–5507. [PubMed]
  • Hahn WC, Menzin E, Saito T, Germain RN, Bierer BE. The complete sequences of plasmids pFNeo and pMH-Neo: convenient expression vectors for high-level expression of eukaryotic genes in hematopoietic cell lines. Gene. 1993 May 30;127(2):267–268. [PubMed]
  • Hsu DK, Zuberi RI, Liu FT. Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin. J Biol Chem. 1992 Jul 15;267(20):14167–14174. [PubMed]
  • Robertson MW, Albrandt K, Keller D, Liu FT. Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. Biochemistry. 1990 Sep 4;29(35):8093–8100. [PubMed]
  • Reed JC, Cuddy M, Haldar S, Croce C, Nowell P, Makover D, Bradley K. BCL2-mediated tumorigenicity of a human T-lymphoid cell line: synergy with MYC and inhibition by BCL2 antisense. Proc Natl Acad Sci U S A. 1990 May;87(10):3660–3664. [PMC free article] [PubMed]
  • Margolskee RF. Epstein-Barr virus based expression vectors. Curr Top Microbiol Immunol. 1992;158:67–95. [PubMed]
  • Liu FT, Orida N. Synthesis of surface immunoglobulin E receptor in Xenopus oocytes by translation of mRNA from rat basophilic leukemia cells. J Biol Chem. 1984 Sep 10;259(17):10649–10652. [PubMed]
  • Liu FT, Hsu DK, Zuberi RI, Kuwabara I, Chi EY, Henderson WR., Jr Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. Am J Pathol. 1995 Oct;147(4):1016–1028. [PMC free article] [PubMed]
  • Buttke TM, McCubrey JA, Owen TC. Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines. J Immunol Methods. 1993 Jan 4;157(1-2):233–240. [PubMed]
  • Hansen MB, Nielsen SE, Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989 May 12;119(2):203–210. [PubMed]
  • Harrington EA, Fanidi A, Evan GI. Oncogenes and cell death. Curr Opin Genet Dev. 1994 Feb;4(1):120–129. [PubMed]
  • Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. [PubMed]
  • Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell. 1995 Jan 27;80(2):279–284. [PubMed]
  • Bertrand R, Solary E, O'Connor P, Kohn KW, Pommier Y. Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res. 1994 Apr;211(2):314–321. [PubMed]
  • Tsujimoto Y. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1958–1962. [PMC free article] [PubMed]
  • Reed JC. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994 Jan;124(1-2):1–6. [PMC free article] [PubMed]
  • Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. [PubMed]
  • Nuñez G, Clarke MF. The Bcl-2 family of proteins: regulators of cell death and survival. Trends Cell Biol. 1994 Nov;4(11):399–403. [PubMed]
  • Hanada M, Aimé-Sempé C, Sato T, Reed JC. Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J Biol Chem. 1995 May 19;270(20):11962–11969. [PubMed]
  • Boise LH, González-García M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 1993 Aug 27;74(4):597–608. [PubMed]
  • Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994 May 26;369(6478):321–323. [PubMed]
  • Herrmann J, Turck CW, Atchison RE, Huflejt ME, Poulter L, Gitt MA, Burlingame AL, Barondes SH, Leffler H. Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase. J Biol Chem. 1993 Dec 15;268(35):26704–26711. [PubMed]
  • Gitt MA, Wiser MF, Leffler H, Herrmann J, Xia YR, Massa SM, Cooper DN, Lusis AJ, Barondes SH. Sequence and mapping of galectin-5, a beta-galactoside-binding lectin, found in rat erythrocytes. J Biol Chem. 1995 Mar 10;270(10):5032–5038. [PubMed]
  • Madsen P, Rasmussen HH, Flint T, Gromov P, Kruse TA, Honoré B, Vorum H, Celis JE. Cloning, expression, and chromosome mapping of human galectin-7. J Biol Chem. 1995 Mar 17;270(11):5823–5829. [PubMed]
  • Hadari YR, Paz K, Dekel R, Mestrovic T, Accili D, Zick Y. Galectin-8. A new rat lectin, related to galectin-4. J Biol Chem. 1995 Feb 17;270(7):3447–3453. [PubMed]
  • Lobsanov YD, Gitt MA, Leffler H, Barondes SH, Rini JM. X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution. J Biol Chem. 1993 Dec 25;268(36):27034–27038. [PubMed]
  • Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. [PubMed]
  • Moutsatsos IK, Davis JM, Wang JL. Endogenous lectins from cultured cells: subcellular localization of carbohydrate-binding protein 35 in 3T3 fibroblasts. J Cell Biol. 1986 Feb;102(2):477–483. [PMC free article] [PubMed]
  • Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y. Multiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res. 1994 May 1;54(9):2468–2471. [PubMed]
  • Raz A, Meromsky L, Zvibel I, Lotan R. Transformation-related changes in the expression of endogenous cell lectins. Int J Cancer. 1987 Mar 15;39(3):353–360. [PubMed]
  • Hébert E, Monsigny M. Oncogenes and expression of endogenous lectins and glycoconjugates. Biol Cell. 1993;79(2):97–109. [PubMed]
  • Hébert E, Monsigny M. Galectin-3 mRNA level depends on transformation phenotype in ras-transformed NIH 3T3 cells. Biol Cell. 1994;81(1):73–76. [PubMed]
  • Copeland KF, Haaksma AG, Goudsmit J, Krammer PH, Heeney JL. Inhibition of apoptosis in T cells expressing human T cell leukemia virus type I Tax. AIDS Res Hum Retroviruses. 1994 Oct;10(10):1259–1268. [PubMed]
  • Perillo NL, Pace KE, Seilhamer JJ, Baum LG. Apoptosis of T cells mediated by galectin-1. Nature. 1995 Dec 14;378(6558):736–739. [PubMed]
  • Boise LH, Gottschalk AR, Quintáns J, Thompson CB. Bcl-2 and Bcl-2-related proteins in apoptosis regulation. Curr Top Microbiol Immunol. 1995;200:107–121. [PubMed]

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