Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
권호 표지

Transcriptional Regulation and Apoptosis Induction by Tcf/$\beta$-Catenin Complex in Various T-Cells

  • Jeong, Sunjoo (Department of Molecular Biology, College of Natural Sciences, Dankook University) ;
  • Lee, Seung-Yeon (Department of Molecular Biology, College of Natural Sciences, Dankook University) ;
  • Lee, Sun-Hee (Department of Molecular Biology, College of Natural Sciences, Dankook University)
  • Published : 2000.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

The Tcf-1 (1-cell factor-1) protein binds to the T-cell specific enhancer sequences and plays an architectural role in the assembly of transcriptional machinery. One of the Tcf family proteins, Tcf-4, was found to be an important regulator for colon cancer development where it activates specific genes upon binding to $\beta$-catenin following Wnt signaling. We were interested in the transcriptional regulatory activities of Tcf-1 and Tcf-4 proteins in T-cells and colon cancer cells. Transactivation assay was developed using a reporter plasmid containing luciferase gene under the control of Tcf responsive elements. Luciferase activity was determined following co-transfection of the reporter along with Tcf-1 and/or $\beta$-catenin expressing plasmids. Transcription was significantly induced by $\beta$-catenin expression in all cells. Tcf-1 by itself did not induce transcription in the mature T-cell lines, but overexpressed Tcf-1 greatly activated transcription in the immature T-cell line. In addition, transfected $\beta$-catenin induced apoptosis, but co-transfected Tcf-1 suppressed apoptosis in HEK293 cells. These results suggest that Tcf-1 and $\beta$-catenin differently regulate transcription and apoptosis.

Keywords

References

  1. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, and Birchmeier W (1996) Functional interaction of ${\beta}$-catenin with the transcription factor LEF-1. Nature 382: 638 https://doi.org/10.1038/382638a0
  2. Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, and Bejsovec A (1998) Drosophila Tcf and Groucho interact to repress wingless signalling activity. Nature 395: 604-612 https://doi.org/10.1038/26982
  3. Clevers H and van de Wetering M (1997) TCF earn their wings. Trends Genet 13: 485-489 https://doi.org/10.1016/S0168-9525(97)01305-X
  4. Fukuda K (1999) Apoptosis-associated cleavage of ${\beta}$-catenin in human colon cancer and rat hepatoma cells. Int J Biochem Cell Biol 31: 519-529 https://doi.org/10.1016/S1357-2725(98)00119-8
  5. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, Costa LTD, Morin PJ, Vogelstein B, and Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281: 1509-1512 https://doi.org/10.1126/science.281.5382.1509
  6. Hernandez-Munain C, Roberts JL, and Krangel MS (1998) Cooperation among multiple trascription factors ls required for access to minimal T-cell receptor ${\alpha}$-enhancer chromatin In vivo. Mol Cell Biol 18: 3223-3233
  7. Hsu SC, Galceran J, and Grosschedl R (1998) Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with ${\beta}$-catenin. Mol Cell Biol 18: 4807-4818
  8. Ishitani T, Ninomiya-Tsuji J, Nagai S, Nishita M, Meneghini M, Barkers N, Waterman M, Bowerman B, Clevers H, Shibuya H, and Matsumoto K (1999) The TAK1-NLK-MAPK-related pathway antogonizes signaling between ${\beta}$-catenin and transcription factor TCF. Nature 399: 798-802 https://doi.org/10.1038/21674
  9. Jeon SH, Jeong SJ, Lee CJ, Kim JK, Kim YS, Chung HY, Park SD, and Seong RH (1998) Expression of Tcf-1 mRNA and surface TCR-CD3 complexes are reduced during apoptosis of T cells. Int Immunol 10: 1519-1527 https://doi.org/10.1093/intimm/10.10.1519
  10. Jeong SJ, Seon SH, Yim JB, Park SD, and Seong RH (1998) Down-regulation of Tcf-1 Expression by activation-induced apoptosis of T cell hybridoma. Korean J Biol Sci 2: 403-410
  11. Kim K, Pang KM, Evans M, and Hay ED (2000) Overexpression of beta-catenin induces apoptosis independent of its transctivation function with LEF-1 or the involvement of major G1 cell cycle. Mol Biol Cell 11: 3509-3523
  12. Korinek V, Barker N, Morin PJ, Wichen DV, Weger RD, Kinzler KW, Vogelstein B, and Clevers H (1997) Constitutive transcriptional activation by a ${\beta}$-catenin-Tcf complex in $APC^{-/-}$ colon carcinoma. Science 275: 1784-1787 https://doi.org/10.1126/science.275.5307.1784
  13. Lee YJ, Swencki B, Shoichet S, and Shivdasani R.A. (1999) A Possible role for the high mobility group box transcrition factor Tcf-4 in vertebrate gut epithelial cell differentiation. J Biol Chem 274: 1566-1572 https://doi.org/10.1074/jbc.274.3.1566
  14. Love JJ, Li X, Case DA, Giese K, Grosschedl R, and Wright P (1995) Structural basis for DNA bendling by the architectural trascription factor LEF-1. Nature 376: 791-795 https://doi.org/10.1038/376791a0
  15. Meneghini MD, Ishitani T, Carter JC, Hisamoto N, Ninomita-Tsuji J, Thorpe CJ, Hamill DR, Matsumoto K, and Bowerman B (1999) MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399: 793-797 https://doi.org/10.1038/21666
  16. Morin PJ (1999) ${\beta}$-catenin signaling and cancer. BioEssays 21: 1021-1030 https://doi.org/10.1002/(SICI)1521-1878(199912)22:1<1021::AID-BIES6>3.0.CO;2-P
  17. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, and Kinzler KW (1997) Activation of ${\beta}$-catenin-Tcf signaling in colon cancer by mutation in ${\beta}$-catenin or APC. Science 275: 1787-1790 https://doi.org/10.1126/science.275.5307.1787
  18. Okamura RM, Sigvardsson M, Galceran J, verbeek S, Clevers H, and Grosschedl R (1998) Redundant regulation of T cell differentiation and TCF-${\alpha}$ gene expression by trascription factors LEF-1 and TCF-1. Immunity 8: 11-20 https://doi.org/10.1016/S1074-7613(00)80454-9
  19. Oosterwegel M, van de Wetering M, Timmerman J, Kruisbeek A, Destree O,Meijink F, and Clevers H (1993) Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis. Development 118: 439-448
  20. Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldchmeding R, Logtenberg T, and Clevers H (1999) Synergy between tumor suppressor APC and the ${\beta}$-catenin-Tcf4 target Tcf1. Science 285: 1923-1926 https://doi.org/10.1126/science.285.5435.1923
  21. Roberts JL, Lauzurica P, and Kragel MS (1997) Developmental regulation of VDJ recombination by the core fragment of the T cell recptor ${\alpha}$ enhancer. J Exp Med 185: 131-140 https://doi.org/10.1084/jem.185.1.131
  22. Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, and Polakis P (1997) Stabilization of ${\beta}$-catenin by genetic defects in melanoma cell lines. Science 275: 1790-1792 https://doi.org/10.1126/science.275.5307.1790
  23. Schilham MW, Wilson A, Moerer P, Bemaissa-Trouw BJ, Cumano A, and Clevers HC (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161: 3984-3991
  24. Staal FJT, Burgering MT, van de Wetering M, and Clevers HC (1999) Tcf-1-mediated transcription in T lymphocytes: differential role for glycogen synthase kinase-3 in fibroblasts and T cells. Int Immunol 11: 317-323 https://doi.org/10.1093/intimm/11.3.317
  25. Tetsu O and McCormick F (1999) ${\beta}$-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398: 422-426 https://doi.org/10.1038/18884
  26. van de Wetering M, Oosterwegel M, Dooiges D, and Clevers H (1991) Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J 10: 123-132
  27. Verbeek S, Izon D, Hofhuis F, Robabus-Maandag E, Riele H, Wetering M, Oosterwegel M, Wilson A, MacDonald HR, and Clevers H (1995) An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374: 70-74 https://doi.org/10.1038/374070a0
  28. Waltzer L and Bienz M (1998) Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395: 521-525 https://doi.org/10.1038/26785