Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Diversity of LEF/TCF action in development and disease

Oncogene volume 25, pages 7492–7504 (2006)Cite this article

Abstract

Lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) mediate Wnt signals in the nucleus by recruiting β-catenin and its co-activators to Wnt response elements (WREs) of target genes. This activity is important during development but its misregulation plays a role in disease such as cancer, where overactive Wnt signaling drives LEF/TCFs to transform cells. The size of the LEF/TCF family is small: approximately four members in vertebrates and one orthologous form in flies, worms and hydra. However, size belies complexity. The LEF/TCF family exhibits extensive patterns of alternative splicing, alternative promoter usage and activities of repression, as well as activation. Recent work from numerous laboratories has highlighted how this complexity has important biological consequences in development and disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP . (2003). A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem 278: 30828–30834.

    Article  CAS  PubMed  Google Scholar 

  • Atcha FA, Munguia JE, Li TW, Hovanes K, Waterman ML . (2003). A new beta -catenin dependent activation domain in T cell factor. J Biol Chem 278: 16169–16175.

    Article  CAS  PubMed  Google Scholar 

  • Balmelle N, Zamarreno N, Krangel MS, Hernandez-Munain C . (2004). Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol 173: 5054–5063.

    Article  CAS  PubMed  Google Scholar 

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R et al. (1996). Functional interaction of b-catenin with the transcription factor LEF-1. Nature 382: 638–642.

    Article  CAS  PubMed  Google Scholar 

  • Beland M, Pilon N, Houle M, Oh K, Sylvestre JR, Prinos P et al. (2004). Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex. Mol Cell Biol 24: 5028–5038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boras K, Hamel PA . (2002). Alx4 binding to LEF-1 regulates N-CAM promoter activity. J Biol Chem 277: 1120–1127.

    Article  CAS  PubMed  Google Scholar 

  • Brannon M, Brown JD, Bates R, Kimelman D, Moon RT . (1999). XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development. Development 126: 3159–3170.

    CAS  PubMed  Google Scholar 

  • Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D . (1997). A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev 11: 2359–2370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brantjes H, Roose J, van De Wetering M, Clevers H . (2001). All TCF HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res 29: 1410–1419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruhn L, Munnerly A, Grosschedl R . (1997). ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCR alpha enhancer function. Genes Dev 11: 640–653.

    Article  CAS  PubMed  Google Scholar 

  • Brunner E, Peter O, Schweizer L, Basler K . (1997). Pangolin encodes a LEF-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature 385: 829–833.

    Article  CAS  PubMed  Google Scholar 

  • Carlsson P, Waterman M, Jones K . (1993). The hLEF/TCF-1a HMG protein contains a context-dependent transcriptional activation domain that induces the TCRa enhancer in T cells. Genes Dev 7: 2418–2430.

    Article  CAS  PubMed  Google Scholar 

  • Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H et al. (1998). Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395: 604–608.

    Article  CAS  PubMed  Google Scholar 

  • Cordray P, Satterwhite DJ . (2005). TGF-beta induces novel Lef-1 splice variants through a Smad-independent signaling pathway. Dev Dyn 232: 969–978.

    Article  CAS  PubMed  Google Scholar 

  • Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA et al. (2001). The PEA3 subfamily of Ets transcription factors synergizes with beta- catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol 21: 1370–1383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuilliere-Dartigues P, El-Bchiri J, Krimi A, Buhard O, Fontanges P, Flejou JF et al. (2006). TCF-4 isoforms absent in TCF-4 mutated MSI-H colorectal cancer cells colocalize with nuclear CtBP and repress TCF-4-mediated transcription. Oncogene 25: 4441–4448.

    Article  CAS  PubMed  Google Scholar 

  • Daniels DL, Weis WI . (2005). Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol 12: 364–371.

    Article  CAS  PubMed  Google Scholar 

  • DasGupta R, Fuchs E . (1999). Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126: 4557–4568.

    CAS  PubMed  Google Scholar 

  • Deltour S, Pinte S, Guerardel C, Wasylyk B, Leprince D . (2002). The human candidate tumor suppressor gene HIC1 recruits CtBP through a degenerate GLDLSKK motif. Mol Cell Biol 22: 4890–4901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorsky RI, Itoh M, Moon RT, Chitnis A . (2003). Two tcf3 genes cooperate to pattern the zebrafish brain. Development 130: 1937–1947.

    Article  CAS  PubMed  Google Scholar 

  • Dorsky RI, Raible DW, Moon RT . (2000). Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway. Genes Dev 14: 158–162.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dorsky RI, Sheldahl LC, Moon RT . (2002). A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development. Dev Biol 241: 229–237.

    Article  CAS  PubMed  Google Scholar 

  • Duval A, Gayet J, Zhou XP, Iacopetta B, Thomas G, Hamelin R . (1999). Frequent frameshift mutations of the TCF-4 gene in colorectal cancers with microsatellite instability. Cancer Res 59: 4213–4215.

    CAS  PubMed  Google Scholar 

  • Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R . (2000). The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines. Cancer Res 60: 3872–3879.

    CAS  PubMed  Google Scholar 

  • El-Tanani M, Platt-Higgins A, Rudland PS, Campbell FC . (2004). Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription. J Biol Chem 279: 20794–20806.

    Article  CAS  PubMed  Google Scholar 

  • Fang M, Li J, Blauwkamp T, Bhambhani C, Campbell N, Cadigan KM . (2006). C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila. EMBO J 25: 2735–2745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galceran J, Farinas I, Depew MJ, Clevers H, Grosschedl R . (1999). Wnt3a−/−−like phenotype and limb deficiency in Lef1(−/−)Tcf1(−/−) mice. Genes Dev 13: 709–717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gay F, Calvo D, Lo MC, Ceron J, Maduro M, Lin R et al. (2003). Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1. Genes Dev 17: 717–722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghogomu SM, van Venrooy S, Ritthaler M, Wedlich D, Gradl D . (2006). HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription. J Biol Chem 281: 1755–1764.

    Article  CAS  PubMed  Google Scholar 

  • Giese K, Amsterdam A, Grosschedl R . (1991). DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1. Genes Dev 5: 2567–2578.

    Article  CAS  PubMed  Google Scholar 

  • Giese K, Cox J, Grosscheldl R . (1992). The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69: 185–196.

    Article  CAS  PubMed  Google Scholar 

  • Giese K, Kingsley C, Kirshner JR, Grosschedl R . (1995). Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein–protein interactions. Genes Dev 9: 995–1008.

    Article  CAS  PubMed  Google Scholar 

  • Gradl D, Konig A, Wedlich D . (2002). Functional diversity of Xenopus lymphoid enhancer factor/T-cell factor transcription factors relies on combinations of activating and repressing elements. J Biol Chem 277: 14159–14171.

    Article  CAS  PubMed  Google Scholar 

  • Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W . (2001). Tcf4 can specifically recognize beta-catenin using alternative conformations. Nat Struct Biol 8: 1048–1052.

    Article  CAS  PubMed  Google Scholar 

  • Graham TA, Weaver C, Mao F, Kimelman D, Xu W . (2000). Crystal structure of a beta-catenin/Tcf complex. Cell 103: 885–896.

    Article  CAS  PubMed  Google Scholar 

  • Grosschedl R, Giese K, Pagel J . (1994). HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10: 94–100.

    Article  CAS  PubMed  Google Scholar 

  • Hamada F, Bienz M . (2004). The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell 7: 677–685.

    Article  CAS  PubMed  Google Scholar 

  • Hammerlein A, Weiske J, Huber O . (2005). A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/beta-catenin complex. Cell Mol Life Sci 62: 606–618.

    Article  CAS  PubMed  Google Scholar 

  • Haremaki T, Tanaka Y, Hongo I, Yuge M, Okamoto H . (2003). Integration of multiple signal transducing pathways on Fgf response elements of the Xenopus caudal homologue Xcad3. Development 130: 4907–4917.

    Article  CAS  PubMed  Google Scholar 

  • Hecht A, Stemmler MP . (2003). Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4. J Biol Chem 278: 3776–3785.

    Article  CAS  PubMed  Google Scholar 

  • Held W, Clevers H, Grosschedl R . (2003). Redundant functions of TCF-1 and LEF-1 during T and NK cell development, but unique role of TCF-1 for Ly49 NK cell receptor acquisition. Eur J Immunol 33: 1393–1398.

    Article  CAS  PubMed  Google Scholar 

  • Hikasa H, Sokol SY . (2004). The involvement of Frodo in TCF-dependent signaling and neural tissue development. Development 131: 4725–4734.

    Article  CAS  PubMed  Google Scholar 

  • Houston DW, Kofron M, Resnik E, Langland R, Destree O, Wylie C et al. (2002). Repression of organizer genes in dorsal and ventral Xenopus cells mediated by maternal XTcf3. Development 129: 4015–4025.

    CAS  PubMed  Google Scholar 

  • Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J et al. (2001). Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28: 53–57.

    CAS  PubMed  Google Scholar 

  • Hovanes K, Li TWH, Waterman ML . (2000). The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing. Nucleic Acids Res 28: 1994–2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu MC, Rosenblum ND . (2005). Smad1, beta-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription. Development 132: 215–225.

    Article  CAS  PubMed  Google Scholar 

  • Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann B, Kemler R . (1996). Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 59: 3–10.

    Article  CAS  PubMed  Google Scholar 

  • Hurlstone A, Clevers H . (2002). T-cell factors: turn-ons and turn-offs. EMBO J 21: 2303–2311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussein SM, Duff EK, Sirard C . (2003). Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J Biol Chem 278: 48805–48814.

    Article  CAS  PubMed  Google Scholar 

  • Ishitani T, Matsumoto K, Chitnis AB, Itoh M . (2005). Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability. Nat Cell Biol 7: 1106–1112.

    Article  CAS  PubMed  Google Scholar 

  • Ishitani T, Ninomiya-Tsuji J, Matsumoto K . (2003). Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling. Mol Cell Biol 23: 1379–1389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishitani T, Ninomiya-Tsuji J, Nagai S, Nishita M, Meneghini M, Barker N et al. (1999). The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature 399: 798–802.

    Article  CAS  PubMed  Google Scholar 

  • Jamora C, DasGupta R, Kocieniewski P, Fuchs E . (2003). Links between signal transduction, transcription and adhesion in epithelial bud development. Nature 422: 317–322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahler RA, Westendorf JJ . (2003). Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J Biol Chem 278: 11937–11944.

    Article  CAS  PubMed  Google Scholar 

  • Kennell JA, O'Leary EE, Gummow BM, Hammer GD, MacDougald OA . (2003). T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol Cell Biol 23: 5366–5375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR et al. (2000). Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin. Genes Dev 14: 1319–1331.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ et al. (1998a). Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19: 379–383.

    Article  CAS  PubMed  Google Scholar 

  • Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, Markman M et al. (1998b). Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse. Mol Cell Biol 18: 1248–1256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunz M, Herrmann M, Wedlich D, Gradl D . (2004). Autoregulation of canonical Wnt signaling controls midbrain development. Dev Biol 273: 390–401.

    Article  CAS  PubMed  Google Scholar 

  • Kusano S, Raab-Traub N . (2002). I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways. Mol Cell Biol 22: 6393–6405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Labbe E, Letamendia A, Attisano L . (2000). Association of Smads with lymphoid enhancer binding factor 1/T cell- specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways. Proc Natl Acad Sci USA 97: 8358–8363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S et al. (1998). Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Proc Natl Acad Sci USA 95: 11590–11595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li TW, Ting JH, Yokoyama NN, Bernstein A, van de Wetering M, Waterman ML . (2006). Wnt activation and alternative promoter repression of LEF1 in colon cancer. Mol Cell Biol 26: 5284–5299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F, van den Broek O, Destree O, Hoppler S . (2005). Distinct roles for Xenopus Tcf/Lef genes in mediating specific responses to Wnt/{beta}-catenin signalling in mesoderm development. Development 132: 5375–5385.

    Article  CAS  PubMed  Google Scholar 

  • Lo MC, Gay F, Odom R, Shi Y, Lin R . (2004). Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans. Cell 117: 95–106.

    Article  CAS  PubMed  Google Scholar 

  • Love JJ, Li X, Case DA, Giese K, Grosschedl R, Wright PE . (1995). Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376: 791–795.

    Article  CAS  PubMed  Google Scholar 

  • Maduro MF, Kasmir JJ, Zhu J, Rothman JH . (2005). The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1 to activate C. elegans endoderm development. Dev Biol 285: 510–523.

    Article  CAS  PubMed  Google Scholar 

  • Meneghini MD, Ishitani T, Carter JC, Hisamoto N, Ninomiya-Tsuji J, Thorpe CJ et al. (1999). MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399: 793–797.

    Article  CAS  PubMed  Google Scholar 

  • Merrill BJ, Gat U, DasGupta R, Fuchs E . (2001). Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev 15: 1688–1705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merrill BJ, Pasolli HA, Polak L, Rendl M, Garcia-Garcia MJ, Anderson KV et al. (2004). Tcf3: a transcriptional regulator of axis induction in the early embryo. Development 131: 263–274.

    Article  CAS  PubMed  Google Scholar 

  • Miravet S, Piedra J, Miro F, Itarte E, Garcia de Herreros A, Dunach M . (2002). The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin. J Biol Chem 277: 1884–1891.

    Article  CAS  PubMed  Google Scholar 

  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V et al. (1996). XTCF-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86: 391–399.

    Article  CAS  PubMed  Google Scholar 

  • Nishita M, Hashimoto MK, Ogata S, Laurent MN, Ueno N, Shibuya H et al. (2000). Interaction between Wnt and TGFβ signalling pathways during formation of Spemann's organizer. Nature 403: 781–783.

    Article  CAS  PubMed  Google Scholar 

  • Okamura R, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R . (1998). Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity 8: 11–20.

    Article  CAS  PubMed  Google Scholar 

  • Oosterwegel M, van de Wetering M, Holstege FC, Prosser HM, Owen MJ, Clevers HC . (1991). TCF-1, a T cell-specific transcription factor of the HMG box family, interacts with sequence motifs in the TCR beta and TCR delta enhancers. Int Immuno 3: 1189–1192.

    Article  CAS  Google Scholar 

  • Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K et al. (2005). Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. Dev Cell 8: 843–854.

    Article  CAS  PubMed  Google Scholar 

  • Payre F, Vincent A, Carreno S . (1999). ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature 400: 271–275.

    Article  CAS  PubMed  Google Scholar 

  • Pereira L, Yi F, Merrill BJ . (2006). Repression of nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal. Mol Cell Biol (E-pub ahead of print).

  • Prieve MG, Guttridge KL, Munguia JE, Waterman ML . (1998). Differential importin-a recognition and nuclear transport by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer factor 1 and T-cell factor 1. Mol Cell Biol 18: 4819–4832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pukrop T, Gradl D, Henningfeld KA, Knochel W, Wedlich D, Kuhl M . (2001). Identification of two regulatory elements within the high mobility group box transcription factor XTCF-4. J Biol Chem 276: 8968–8978.

    Article  CAS  PubMed  Google Scholar 

  • Riese J, Yu X, Munnerlyn A, Eresh S, Hsu SC, Grosschedl R et al. (1997). LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88: 777–787.

    Article  CAS  PubMed  Google Scholar 

  • Roel G, Hamilton FS, Gent Y, Bain AA, Destree O, Hoppler S . (2002). Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt signaling during Xenopus development. Curr Biol 12: 1941–1945.

    Article  CAS  PubMed  Google Scholar 

  • Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R et al. (1999). Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science 285: 1923–1926.

    Article  CAS  PubMed  Google Scholar 

  • Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P et al. (1998). The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395: 608–612.

    Article  CAS  PubMed  Google Scholar 

  • Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R . (2001). PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev 15: 3088–3103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito H, Yasumoto K, Takeda K, Takahashi K, Fukuzaki A, Orikasa S et al. (2002). Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1. J Biol Chem 277: 28787–28794.

    Article  CAS  PubMed  Google Scholar 

  • Sheridan PL, Sheline CT, Cannon K, Voz ML, Pazin MJ et al. (1995). Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro. Genes Dev 9: 2090–2104.

    Article  CAS  PubMed  Google Scholar 

  • Shetty P, Lo MC, Robertson SM, Lin R . (2005). C. elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels. Dev Biol 285: 584–592.

    Article  CAS  PubMed  Google Scholar 

  • Shulewitz M, Soloviev I, Wu T, Koeppen H, Polakis P, Sakanaka C . (2006). Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer. Oncogene 25: 4361–4369.

    Article  CAS  PubMed  Google Scholar 

  • Sierra J, Yoshida T, Joazeiro CA, Jones KA . (2006). The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev 20: 586–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snider L, Tapscott SJ . (2005). XIC is required for Siamois activity and dorsoanterior development. Mol Cell Biol 25: 5061–5072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snider L, Thirlwell H, Miller JR, Moon RT, Groudine M, Tapscott SJ . (2001). Inhibition of Tcf3 binding by I-mfa domain proteins. Mol Cell Biol 21: 1866–1873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spring CM, Kelly KF, O'Kelly I, Graham M, Crawford HC, Daniel JM . (2005). The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. Exp Cell Res 305: 253–265.

    Article  CAS  PubMed  Google Scholar 

  • Standley HJ, Destree O, Kofron M, Wylie C, Heasman J . (2006). Maternal XTcf1 and XTcf4 have distinct roles in regulating Wnt target genes. Dev Biol 289: 318–328.

    Article  CAS  PubMed  Google Scholar 

  • Stankovic-Valentin N, Verger A, Deltour-Balerdi S, Quinlan KG, Crossley M, Leprince D . (2006). A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP. FEBS J 273: 2879–2890.

    Article  CAS  PubMed  Google Scholar 

  • Takeda H, Lyle S, Lazar AJ, Zouboulis CC, Smyth I, Watt FM . (2006). Human sebaceous tumors harbor inactivating mutations in LEF1. Nat Med 12: 395–397.

    Article  CAS  PubMed  Google Scholar 

  • Theisen H, Haerry TE, O'Connor MB, Marsh JL . (1996). Developmental territories created by mutual antagonism between wingless and decapentaplegic. Development 122: 3939–3948.

    CAS  PubMed  Google Scholar 

  • Tutter AV, Fryer CJ, Jones KA . (2001). Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro. Genes Dev 15: 3342–3354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadlamudi U, Espinoza HM, Ganga M, Martin DM, Liu X, Engelhardt JF et al. (2005). PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. J Cell Sci 118: 1129–1137.

    Article  CAS  PubMed  Google Scholar 

  • Valenta T, Lukas J, Doubravska L, Fafilek B, Korinek V . (2006). HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-catenin to the nuclear bodies. EMBO J 25: 2326–2337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valenta T, Lukas J, Korinek V . (2003). HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells. Nucleic Acids Res 31: 2369–2380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Beest M, Dooijes D, van De Wetering M, Kjaerulff S, Bonvin A, Nielsen O et al. (2000). Sequence-specific high mobility group box factors recognize 10–12-base pair minor groove motifs. J Biol Chem 275: 27266–27273.

    CAS  PubMed  Google Scholar 

  • van de Wetering M, Castrop J, Korinek V, Clevers H . (1996). Extensive alternative splicing and dual promoter usage generate Tcf-protein isoforms with differential transcription control properties. Mol Cell Biol 16: 745–752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J et al. (1997). Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88: 789–799.

    Article  CAS  PubMed  Google Scholar 

  • van de Wetering M, Clevers H . (1992). Sequence-specific interaction of the HMG box proteins TCF-1 and SRY occurs within the minor groove of a Watson–Crick double helix. EMBO J 11: 3039–3044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Genderen C, Okamura R, Farinas I, Quo R, Parslow T, Bruhn L et al. (1994). Development of several organs that require inductive epithelial–mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev 8: 2691–2703.

    Article  CAS  PubMed  Google Scholar 

  • van Noort M, Clevers H . (2002). TCF transcription factors, mediators of Wnt-signaling in development and cancer. Dev Biol 244: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • van Roy FM, McCrea PD . (2005). A role for Kaiso-p120ctn complexes in cancer? Nat Rev Cancer 5: 956–964.

    Article  CAS  PubMed  Google Scholar 

  • Veien ES, Grierson MJ, Saund RS, Dorsky RI . (2005). Expression pattern of zebrafish tcf7 suggests unexplored domains of Wnt/beta-catenin activity. Dev Dyn 233: 233–239.

    Article  CAS  PubMed  Google Scholar 

  • Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, te Riele H, van de Wetering M et al. (1995). An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374: 70–74.

    Article  CAS  PubMed  Google Scholar 

  • Waltzer L, Bienz M . (1998). Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395: 521–525.

    Article  CAS  PubMed  Google Scholar 

  • Waterman ML . (2004). Lymphoid enhancer factor/T cell factor expression in colorectal cancer. Cancer Metastasis Rev 23: 41–52.

    Article  CAS  PubMed  Google Scholar 

  • Weerkamp F, Baert MR, Naber BA, Koster EE, de Haas EF, Atkuri KR et al. (2006). Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules. Proc Natl Acad Sci USA 103: 3322–3326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willert K, Jones KA . (2006). Wnt signaling: is the party in the nucleus? Genes Dev 20: 1394–1404.

    Article  CAS  PubMed  Google Scholar 

  • Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael AJ, Callan MF . (2006). Human naive CD8T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo. J Immunol 176: 1439–1446.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto H, Ihara M, Matsuura Y, Kikuchi A . (2003). Sumoylation is involved in beta-catenin-dependent activation of Tcf-4. EMBO J 22: 2047–2059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S . (2002). Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling. EMBO J 21: 2703–2714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhurinsky J, Shtutman M, Ben-Ze'ev A . (2000). Differential mechanisms of LEF/TCF family-dependent transcriptional activation by beta-catenin and plakoglobin. Mol Cell Biol 20: 4238–4252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We extend sincere apologies to those whose work is not included due to length constraints on the review. We thank Drs Marianne Bienz, Ken Cadigan, Stefan Hoppler, Tohru Ishitani, Harry Mangalam, Pierre McCrea, Rob Steele, Bill Weis, and Jennifer Westendorf for communications and/or critique. We also thank members of the Waterman, Marsh and Holcombe laboratories at UC, Irvine, for stimulating discussions. MLW was supported by NIH CA83982 and CA096878. LA is supported by the NIH MARC (Minority Access to Research Careers) predoctoral fellowship (GM064210).

Author information

Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA

    L Arce, N N Yokoyama & M L Waterman

Authors
  1. L Arce
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N N Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M L Waterman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M L Waterman.

Additional information

Note added in proof

A commentary by S Hoppler and CL Kavanagh (Wnt signalling: variety at the core. J Cell Sci (2006) (in press)) on the biological consequences of TCF/LEF diversity in vertebrates will appear in an upcoming issue of Journal of Cell Science.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arce, L., Yokoyama, N. & Waterman, M. Diversity of LEF/TCF action in development and disease. Oncogene 25, 7492–7504 (2006). https://doi.org/10.1038/sj.onc.1210056

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210056

Keywords

This article is cited by

Search

Advanced search

Quick links