Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jun 25;93(13):6737–6742. doi: 10.1073/pnas.93.13.6737

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

R Y Yang 1, D K Hsu 1, F T Liu 1
PMCID: PMC39096  PMID: 8692888

Abstract

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.

Full text

PDF
6737

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agrwal N., Wang J. L., Voss P. G. 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] [Google Scholar]
  2. 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] [Google Scholar]
  3. Barondes S. H., Castronovo V., Cooper D. N., Cummings R. D., Drickamer K., Feizi T., Gitt M. A., Hirabayashi J., Hughes C., Kasai K. Galectins: a family of animal beta-galactoside-binding lectins. Cell. 1994 Feb 25;76(4):597–598. doi: 10.1016/0092-8674(94)90498-7. [DOI] [PubMed] [Google Scholar]
  4. Barondes S. H., Cooper D. N., Gitt M. A., Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994 Aug 19;269(33):20807–20810. [PubMed] [Google Scholar]
  5. Bertrand R., Solary E., O'Connor P., Kohn K. W., Pommier Y. Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res. 1994 Apr;211(2):314–321. doi: 10.1006/excr.1994.1093. [DOI] [PubMed] [Google Scholar]
  6. Boise L. H., González-García M., Postema C. E., Ding L., Lindsten T., Turka L. A., Mao X., Nuñez G., Thompson C. B. 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. doi: 10.1016/0092-8674(93)90508-n. [DOI] [PubMed] [Google Scholar]
  7. Boise L. H., Gottschalk A. R., Quintáns J., Thompson C. B. Bcl-2 and Bcl-2-related proteins in apoptosis regulation. Curr Top Microbiol Immunol. 1995;200:107–121. doi: 10.1007/978-3-642-79437-7_8. [DOI] [PubMed] [Google Scholar]
  8. Buttke T. M., McCubrey J. A., Owen T. C. 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. doi: 10.1016/0022-1759(93)90092-l. [DOI] [PubMed] [Google Scholar]
  9. Cleary M. L., Smith S. D., 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. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  10. Copeland K. F., Haaksma A. G., Goudsmit J., Krammer P. H., Heeney J. L. 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. doi: 10.1089/aid.1994.10.1259. [DOI] [PubMed] [Google Scholar]
  11. Cowles E. A., Agrwal N., Anderson R. L., Wang J. L. Carbohydrate-binding protein 35. Isoelectric points of the polypeptide and a phosphorylated derivative. J Biol Chem. 1990 Oct 15;265(29):17706–17712. [PubMed] [Google Scholar]
  12. Crittenden S. L., Roff C. F., Wang J. L. Carbohydrate-binding protein 35: identification of the galactose-specific lectin in various tissues of mice. Mol Cell Biol. 1984 Jul;4(7):1252–1259. doi: 10.1128/mcb.4.7.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dagher S. F., Wang J. L., Patterson R. J. 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. doi: 10.1073/pnas.92.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Flotte T. J., Springer T. A., Thorbecke G. J. 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] [Google Scholar]
  15. Frigeri L. G., Liu F. T. 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] [Google Scholar]
  16. Gitt M. A., Wiser M. F., Leffler H., Herrmann J., Xia Y. R., Massa S. M., Cooper D. N., Lusis A. J., Barondes S. H. 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. doi: 10.1074/jbc.270.10.5032. [DOI] [PubMed] [Google Scholar]
  17. Gritzmacher C. A., Robertson M. W., Liu F. T. IgE-binding protein. Subcellular location and gene expression in many murine tissues and cells. J Immunol. 1988 Oct 15;141(8):2801–2806. [PubMed] [Google Scholar]
  18. Hadari Y. R., 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. doi: 10.1074/jbc.270.7.3447. [DOI] [PubMed] [Google Scholar]
  19. Hahn W. C., Menzin E., Saito T., Germain R. N., Bierer B. E. 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. doi: 10.1016/0378-1119(93)90731-h. [DOI] [PubMed] [Google Scholar]
  20. Hanada M., Aimé-Sempé C., Sato T., Reed J. C. 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. doi: 10.1074/jbc.270.20.11962. [DOI] [PubMed] [Google Scholar]
  21. Hansen M. B., Nielsen S. E., 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. doi: 10.1016/0022-1759(89)90397-9. [DOI] [PubMed] [Google Scholar]
  22. Harrington E. A., Fanidi A., Evan G. I. Oncogenes and cell death. Curr Opin Genet Dev. 1994 Feb;4(1):120–129. doi: 10.1016/0959-437x(94)90100-7. [DOI] [PubMed] [Google Scholar]
  23. Herrmann J., Turck C. W., Atchison R. E., Huflejt M. E., Poulter L., Gitt M. A., Burlingame A. L., Barondes S. H., 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] [Google Scholar]
  24. Hsu D. K., Hammes S. R., Kuwabara I., Greene W. C., Liu F. T. 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] [Google Scholar]
  25. Hsu D. K., Zuberi R. I., Liu F. T. 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] [Google Scholar]
  26. 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. doi: 10.1016/0248-4900(94)90057-4. [DOI] [PubMed] [Google Scholar]
  27. Hébert E., Monsigny M. Oncogenes and expression of endogenous lectins and glycoconjugates. Biol Cell. 1993;79(2):97–109. doi: 10.1111/j.1768-322x.1993.tb00899.x. [DOI] [PubMed] [Google Scholar]
  28. Krajewski S., Krajewska M., Shabaik A., Wang H. G., Irie S., Fong L., Reed J. C. Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res. 1994 Nov 1;54(21):5501–5507. [PubMed] [Google Scholar]
  29. Lindstedt R., Apodaca G., Barondes S. H., Mostov K. E., 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] [Google Scholar]
  30. Liu F. T., Hsu D. K., Zuberi R. I., Kuwabara I., Chi E. Y., Henderson W. R., 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] [Google Scholar]
  31. Liu F. T. Molecular biology of IgE-binding protein, IgE-binding factors, and IgE receptors. Crit Rev Immunol. 1990;10(3):289–306. [PubMed] [Google Scholar]
  32. Liu F. T., 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] [Google Scholar]
  33. Liu F. T. S-type mammalian lectins in allergic inflammation. Immunol Today. 1993 Oct;14(10):486–490. doi: 10.1016/0167-5699(93)90263-K. [DOI] [PubMed] [Google Scholar]
  34. Lobsanov Y. D., Gitt M. A., Leffler H., Barondes S. H., Rini J. M. 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. doi: 10.2210/pdb1hlc/pdb. [DOI] [PubMed] [Google Scholar]
  35. Madsen P., Rasmussen H. H., Flint T., Gromov P., Kruse T. A., Honoré B., Vorum H., Celis J. E. Cloning, expression, and chromosome mapping of human galectin-7. J Biol Chem. 1995 Mar 17;270(11):5823–5829. doi: 10.1074/jbc.270.11.5823. [DOI] [PubMed] [Google Scholar]
  36. Margolskee R. F. Epstein-Barr virus based expression vectors. Curr Top Microbiol Immunol. 1992;158:67–95. doi: 10.1007/978-3-642-75608-5_4. [DOI] [PubMed] [Google Scholar]
  37. Moutsatsos I. K., Davis J. M., Wang J. L. Endogenous lectins from cultured cells: subcellular localization of carbohydrate-binding protein 35 in 3T3 fibroblasts. J Cell Biol. 1986 Feb;102(2):477–483. doi: 10.1083/jcb.102.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Moutsatsos I. K., Wade M., Schindler M., Wang J. L. 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. doi: 10.1073/pnas.84.18.6452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  40. Nuñez G., Clarke M. F. The Bcl-2 family of proteins: regulators of cell death and survival. Trends Cell Biol. 1994 Nov;4(11):399–403. doi: 10.1016/0962-8924(94)90053-1. [DOI] [PubMed] [Google Scholar]
  41. Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. doi: 10.1016/0092-8674(93)90509-o. [DOI] [PubMed] [Google Scholar]
  42. Perillo N. L., Pace K. E., Seilhamer J. J., Baum L. G. Apoptosis of T cells mediated by galectin-1. Nature. 1995 Dec 14;378(6558):736–739. doi: 10.1038/378736a0. [DOI] [PubMed] [Google Scholar]
  43. 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. doi: 10.1002/ijc.2910390314. [DOI] [PubMed] [Google Scholar]
  44. Raz A., Zhu D. G., 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. doi: 10.1002/ijc.2910460520. [DOI] [PubMed] [Google Scholar]
  45. Reed J. C. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994 Jan;124(1-2):1–6. doi: 10.1083/jcb.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Reed J. C., 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. doi: 10.1073/pnas.87.10.3660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Robertson M. W., Albrandt K., Keller D., Liu F. T. 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. doi: 10.1021/bi00487a015. [DOI] [PubMed] [Google Scholar]
  48. Sato S., Burdett I., Hughes R. C. 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. doi: 10.1006/excr.1993.1157. [DOI] [PubMed] [Google Scholar]
  49. Sato S., Hughes R. C. 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] [Google Scholar]
  50. Takayama S., Sato T., Krajewski S., Kochel K., Irie S., Millan J. A., Reed J. C. 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. doi: 10.1016/0092-8674(95)90410-7. [DOI] [PubMed] [Google Scholar]
  51. Thompson C. B. Apoptosis in the pathogenesis and treatment of disease. Science. 1995 Mar 10;267(5203):1456–1462. doi: 10.1126/science.7878464. [DOI] [PubMed] [Google Scholar]
  52. 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. doi: 10.1073/pnas.86.6.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yin X. M., Oltvai Z. N., Korsmeyer S. J. 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. doi: 10.1038/369321a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES