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Regulation of canonical Wnt/β-catenin pathway in the nucleus

  • Review
  • Oncology
  • Published:
Chinese Science Bulletin

Abstract

Canonical Wnt/β-catenin pathway plays a central role in development, homeostasis, as well as tumorigenesis. The regulation of the pathway involves various and complicated mechanisms, including the extracellular, intracellular and endonuclear regulation. As the key component of the pathway, the Lef1/Tcfs-β-catenin complex is also the key target of regulation in the nucleus. In the current review, we are going to summarize the regulators in the nucleus which can modify the transcriptional activity of the Wnt/β-catenin pathway.

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References

  1. Kohn AD, Moon RT (2005) Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium 38:439–446

    Article  Google Scholar 

  2. Chinnadurai G (2002) CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell 9:213–224

    Article  Google Scholar 

  3. Kim W, Kim M, Jho EH (2013) Wnt/beta-catenin signalling: from plasma membrane to nucleus. Biochem J 450:9–21

    Article  Google Scholar 

  4. de Sousa EM, Vermeulen L, Richel D et al (2011) Targeting Wnt signaling in colon cancer stem cells. Clin Cancer Res 17:647–653

    Article  Google Scholar 

  5. Peifer M, Polakis P (2000) Wnt signaling in oncogenesis and embryogenesis—a look outside the nucleus. Science 287:1606–1609

    Article  Google Scholar 

  6. Vacik T, Lemke G (2011) Dominant-negative isoforms of Tcf/Lef proteins in development and disease. Cell Cycle 10:4199–4200

    Article  Google Scholar 

  7. Mao CD, Byers SW (2011) Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials. Crit Rev Eukaryot Gene Expr 21:207–236

    Article  Google Scholar 

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

    Article  Google Scholar 

  9. Stamos JL, Weis WI (2013) The beta-catenin destruction complex. Cold Spring Harb Perspect Biol 5:a007898

    Article  Google Scholar 

  10. Sokol SY (2011) Wnt signaling through T-cell factor phosphorylation. Cell Res 21:1002–1012

    Article  Google Scholar 

  11. Fiedler M, Sanchez-Barrena MJ, Nekrasov M et al (2008) Decoding of methylated histone H3 tail by the Pygo–BCL9 Wnt signaling complex. Mol Cell 30:507–518

    Article  Google Scholar 

  12. Cantu C, Valenta T, Hausmann G et al (2013) The Pygo2–H3K4me2/3 interaction is dispensable for mouse development and Wnt signaling-dependent transcription. Development 140:2377–2386

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. Elfert S, Weise A, Bruser K et al (2013) Acetylation of human TCF4 (TCF7L2) proteins attenuates inhibition by the HBP1 repressor and induces a conformational change in the TCF4: DNA complex. PLoS One 8:e61867

    Article  Google Scholar 

  15. Ota S, Ishitani S, Shimizu N et al (2012) NLK positively regulates Wnt/beta-catenin signalling by phosphorylating LEF1 in neural progenitor cells. EMBO J 31:1904–1915

    Article  Google Scholar 

  16. Bauer A, Huber O, Kemler R (1998) Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein. Proc Natl Acad Sci USA 95:14787–14792

    Article  Google Scholar 

  17. Carlson ML, Wilson ET, Prescott SM (2003) Regulation of COX-2 transcription in a colon cancer cell line by Pontin52/TIP49a. Mol Cancer 2:42

    Article  Google Scholar 

  18. Togi S, Ikeda O, Kamitani S et al (2011) Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem 286:19170–19177

    Article  Google Scholar 

  19. Benchabane H, Xin N, Tian A et al (2011) Jerky/Earthbound facilitates cell-specific Wnt/Wingless signalling by modulating beta-catenin-TCF activity. EMBO J 30:1444–1458

    Article  Google Scholar 

  20. Jennings BH, Ish-Horowicz D (2008) The Groucho/TLE/Grg family of transcriptional co-repressors. Genome Biol 9:205

    Article  Google Scholar 

  21. Brantjes H, Roose J, van De WM et al (2001) All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res 29:1410–1419

    Article  Google Scholar 

  22. Grigoletto A, Lestienne P, Rosenbaum J (2011) The multifaceted proteins Reptin and Pontin as major players in cancer. Biochim Biophys Acta 1815:147–157

    Google Scholar 

  23. Bauer A, Chauvet S, Huber O et al (2000) Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J 19:6121–6130

    Article  Google Scholar 

  24. Gallant P (2007) Control of transcription by pontin and reptin. Trends Cell Biol 17:187–192

    Article  Google Scholar 

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

    Google Scholar 

  26. 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  Google Scholar 

  27. Yamada M, Ohnishi J, Ohkawara B et al (2006) NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF). J Biol Chem 281:20749–20760

    Article  Google Scholar 

  28. Dai L, Aye TC, Liu XY et al (2012) TAK1, more than just innate immunity. IUBMB Life 64:825–834

    Article  Google Scholar 

  29. Tago K, Nakamura T, Nishita M et al (2000) Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev 14:1741–1749

    Google Scholar 

  30. Takemaru K, Yamaguchi S, Lee YS et al (2003) Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 422:905–909

    Article  Google Scholar 

  31. Wu Y, Zhang Y, Zhang H et al (2010) p15RS attenuates Wnt/β-catenin signaling by disrupting β-catenin TCF4 Interaction. J Biol Chem 285:34621–34631

    Article  Google Scholar 

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

    Article  Google Scholar 

  33. Del Valle-Perez B, Casagolda D, Lugilde E et al (2011) Wnt controls the transcriptional activity of Kaiso through CK1epsilon-dependent phosphorylation of p120-catenin. J Cell Sci 124:2298–2309

    Article  Google Scholar 

  34. Liu JA, Wu MH, Yan CH et al (2013) Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling. Proc Natl Acad Sci USA 110:2882–2887

    Article  Google Scholar 

  35. Topol L, Chen W, Song H et al (2009) Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus. J Biol Chem 284:3323–3333

    Article  Google Scholar 

  36. Panza A, Pazienza V, Ripoli M et al (2013) Interplay between SOX9, beta-catenin and PPARgamma activation in colorectal cancer. Biochim Biophys Acta 1833:1853–1865

    Article  Google Scholar 

  37. Brembeck FH, Wiese M, Zatula N et al (2011) BCL9-2 promotes early stages of intestinal tumor progression. Gastroenterology 141:1359–1370

    Article  Google Scholar 

  38. Zhou SY, Xu ML, Wang SQ et al (2014) Overexpression of Pygopus-2 is required for canonical Wnt activation in human lung cancer. Oncol Lett 7:233–238

    Google Scholar 

  39. Li J, Sutter C, Parker DS et al (2007) CBP/p300 are bimodal regulators of Wnt signaling. EMBO J 26:2284–2294

    Article  Google Scholar 

  40. Jessen S, Gu B, Dai X (2008) Pygopus and the Wnt signaling pathway: a diverse set of connections. Bioessays 30:448–456

    Article  Google Scholar 

  41. Fang M, Li J, Blauwkamp T et al (2006) C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila. EMBO J 25:2735–2745

    Article  Google Scholar 

  42. MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26

    Article  Google Scholar 

  43. Arce L, Yokoyama NN, Waterman ML (2006) Diversity of LEF/TCF action in development and disease. Oncogene 25:7492–7504

    Article  Google Scholar 

  44. Moon RT, Kohn AD, De Ferrari GV et al (2004) WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 5:691–701

    Article  Google Scholar 

  45. Grossmann TN, Yeh JT, Bowman BR et al (2012) Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin. Proc Natl Acad Sci USA 109:17942–17947

    Article  Google Scholar 

  46. Paul S, Dey A (2008) Wnt signaling and cancer development: therapeutic implication. Neoplasma 55:165–176

    Google Scholar 

  47. Khan O, La Thangue NB (2012) HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol Cell Biol 90:85–94

    Article  Google Scholar 

  48. Henderson WR Jr, Chi EY, Ye X et al (2010) Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci USA 107:14309–14314

  49. Tian W, Han X, Yan M et al (2012) Structure-based discovery of a novel inhibitor targeting the beta-catenin/Tcf4 interaction. Biochemistry 51:724–731

    Article  Google Scholar 

  50. Li X, Pu J, Jiang S et al (2013) Henryin, an ent-kaurane diterpenoid, inhibits Wnt signaling through interference with beta-catenin/TCF4 interaction in colorectal cancer cells. PLoS One 8:e68525

    Article  Google Scholar 

  51. Wei W, Chua MS, Grepper S et al (2010) Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer 126:2426–2436

    Google Scholar 

  52. Lazarova DL, Chiaro C, Wong T et al (2013) CBP activity mediates effects of the histone deacetylase inhibitor butyrate on WNT activity and apoptosis in colon cancer cells. J Cancer 4:481–490

    Article  Google Scholar 

  53. Richon VM (2010) Targeting histone deacetylases: development of vorinostat for the treatment of cancer. Epigenomics 2:457–465

    Article  Google Scholar 

Download references

Acknowledgement

This work was supported by the National Nature Science Foundation of China (81172034).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Wenxiao Han & Hongying Wang

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  1. Wenxiao Han
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  2. Hongying Wang
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Correspondence to Hongying Wang.

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Han, W., Wang, H. Regulation of canonical Wnt/β-catenin pathway in the nucleus. Chin. Sci. Bull. 59, 3530–3535 (2014). https://doi.org/10.1007/s11434-014-0489-x

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  • DOI: https://doi.org/10.1007/s11434-014-0489-x

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