Home LiteratureArticle Details
PMID: 18339531 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Wnt/beta-catenin signaling: new (and old) players and new insights.

Current opinion in cell biology ·Vol. 20 ·No. 2 ·2008-04-00 ·Pages 119-25

Huang H, He X

Abstract

Wnt/beta-catenin signaling has central roles in embryogenesis and human diseases including cancer. A central scheme of the Wnt pathway is to stabilize the transcription coactivator beta-catenin by preventing its phosphorylation-dependent degradation. Significant progress has been made toward the understanding of this crucial regulatory pathway, including the protein complex that promotes beta-catenin phosphorylation-degradation, and the mechanism by which the extracellular Wnt ligand engages cell surface receptors to inhibit beta-catenin phosphorylation-degradation. Here we review some recent discoveries in these two areas, and highlight some crucial questions that remain to be resolved.

MeSH Terms
Animals Axin Protein Humans Protein Processing, Post-Translational Repressor Proteins/metabolism Signal Transduction Tumor Suppressor Proteins/metabolism Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
Axin Protein Repressor Proteins Tumor Suppressor Proteins Wnt Proteins beta Catenin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Huang He
The F M Kirby Neurobiology Center, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
He Xi
References (51)
51 references, click to expand
  1. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes.
    Genes Dev. 2006 Mar 1;20(5):586-600 PMID: 16510874
  2. Adenomatous polyposis coli proteins and cell adhesion.
    Curr Opin Cell Biol. 2004 Oct;16(5):528-35 PMID: 15363803
  3. Adenomatous polyposis coli tumor suppressor protein has signaling activity in Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior axis.
    J Cell Biol. 1997 Jan 27;136(2):411-20 PMID: 9015311
  4. A critical role for endocytosis in Wnt signaling.
    BMC Cell Biol. 2006 Jul 06;7:28 PMID: 16824228
  5. Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs.
    Dev Biol. 2002 Oct 1;250(1):91-100 PMID: 12297098
  6. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4.
    Science. 2003 Sep 5;301(5638):1391-4 PMID: 12958364
  7. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.
    Mol Cell. 2001 Apr;7(4):801-9 PMID: 11336703
  8. Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP.
    Development. 2004 Oct;131(20):5103-15 PMID: 15459103
  9. Wnt/beta-catenin signaling in development and disease.
    Cell. 2006 Nov 3;127(3):469-80 PMID: 17081971
  10. Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification.
    J Cell Biol. 2000 Feb 21;148(4):691-702 PMID: 10684251
  11. WNT and beta-catenin signalling: diseases and therapies.
    Nat Rev Genet. 2004 Sep;5(9):691-701 PMID: 15372092
  12. Maintaining epithelial integrity: a function for gigantic spectraplakin isoforms in adherens junctions.
    J Cell Biol. 2003 Sep 29;162(7):1305-15 PMID: 14517208
  13. Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development.
    Development. 2002 Apr;129(7):1751-62 PMID: 11923210
  14. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon.
    J Biol Chem. 2001 Oct 19;276(42):39037-45 PMID: 11487578
  15. A mechanism for Wnt coreceptor activation.
    Mol Cell. 2004 Jan 16;13(1):149-56 PMID: 14731402
  16. Dual positive and negative regulation of wingless signaling by adenomatous polyposis coli.
    Science. 2008 Jan 18;319(5861):333-6 PMID: 18202290
  17. Protein phosphatase 1--targeted in many directions.
    J Cell Sci. 2002 Jan 15;115(Pt 2):241-56 PMID: 11839776
  18. Colorectal cancer and genetic alterations in the Wnt pathway.
    Oncogene. 2006 Dec 4;25(57):7531-7 PMID: 17143297
  19. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro.
    Cancer Res. 1994 Jul 15;54(14):3676-81 PMID: 8033083
  20. Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6.
    FEBS Lett. 2008 Jan 23;582(2):255-61 PMID: 18083125
  21. Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.
    Nature. 2005 Dec 8;438(7069):867-72 PMID: 16341016
  22. Plakins: a family of versatile cytolinker proteins.
    Trends Cell Biol. 2002 Jan;12(1):37-45 PMID: 11854008
  23. Regulation of wingless signaling by the CKI family in Drosophila limb development.
    Dev Biol. 2006 Nov 1;299(1):221-37 PMID: 16987508
  24. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling.
    Science. 2007 May 18;316(5827):1043-6 PMID: 17510365
  25. Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.
    J Biol Chem. 1999 Apr 16;274(16):10681-4 PMID: 10196136
  26. Transcription under the control of nuclear Arm/beta-catenin.
    Curr Biol. 2006 May 23;16(10):R378-85 PMID: 16713950
  27. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way.
    Development. 2004 Apr;131(8):1663-77 PMID: 15084453
  28. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex.
    EMBO J. 2007 Mar 21;26(6):1511-21 PMID: 17318175
  29. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway.
    Genes Dev. 2006 Jul 15;20(14):1933-45 PMID: 16815997
  30. Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines.
    Dev Cell. 2007 Jun;12(6):957-71 PMID: 17543867
  31. The Wnt signaling pathway in development and disease.
    Annu Rev Cell Dev Biol. 2004;20:781-810 PMID: 15473860
  32. Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover.
    Nat Cell Biol. 2000 Sep;2(9):653-60 PMID: 10980707
  33. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor.
    Science. 2007 Feb 2;315(5812):642-5 PMID: 17204608
  34. Dynamic recruitment of axin by Dishevelled protein assemblies.
    J Cell Sci. 2007 Jul 15;120(Pt 14):2402-12 PMID: 17606995
  35. AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane.
    J Cell Sci. 2007 Nov 1;120(Pt 21):3738-47 PMID: 17925383
  36. Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization.
    J Cell Biol. 2005 Sep 12;170(6):895-901 PMID: 16157700
  37. Wnt signaling and cancer.
    Genes Dev. 2000 Aug 1;14(15):1837-51 PMID: 10921899
  38. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration.
    J Cell Biol. 1996 Jul;134(1):165-79 PMID: 8698812
  39. beta-catenin destruction complex: insights and questions from a structural perspective.
    Oncogene. 2006 Dec 4;25(57):7482-91 PMID: 17143292
  40. The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization.
    Nat Struct Mol Biol. 2007 Jun;14(6):484-92 PMID: 17529994
  41. Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin.
    Dev Cell. 2006 Aug;11(2):213-23 PMID: 16890161
  42. Truncated mutants of the putative Wnt receptor LRP6/Arrow can stabilize beta-catenin independently of Frizzled proteins.
    Oncogene. 2004 Jun 17;23(28):4873-84 PMID: 15064719
  43. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.
    Genes Dev. 1999 Jul 15;13(14):1768-73 PMID: 10421629
  44. The APC tumour suppressor has a nuclear export function.
    Nature. 2000 Aug 31;406(6799):1009-12 PMID: 10984057
  45. Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.
    Mol Cell. 2003 Nov;12(5):1251-60 PMID: 14636582
  46. Adenomatous polyposis coli (APC) differentially regulates beta-catenin phosphorylation and ubiquitination in colon cancer cells.
    J Biol Chem. 2006 Jun 30;281(26):17751-7 PMID: 16798748
  47. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation.
    Science. 2007 Jun 15;316(5831):1619-22 PMID: 17569865
  48. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions.
    Development. 2008 Jan;135(2):367-75 PMID: 18077588
  49. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
    Nature. 2005 Dec 8;438(7069):873-7 PMID: 16341017
  50. Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP.
    Dev Biol. 2007 Jun 1;306(1):94-111 PMID: 17433287
  51. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway.
    PLoS Biol. 2003 Oct;1(1):E10 PMID: 14551908
Article Info
Journal
Current opinion in cell biology
Abbr.
Curr Opin Cell Biol
ISSN
0955-0674
DOI
10.1016/j.ceb.2008.01.009
Published
2008-04-00
Epub
2008-00-12
Pages
119-25
Language
English
Region
England
NLM ID
8913428
PMCID
PMC2390924
Subset
IM
Grants
NIGMS NIH HHS · R01 GM074241 · United States
NIGMS NIH HHS · R01 GM074241-03 · United States
External Links
PubMed source DOI: 10.1016/j.ceb.2008.01.009 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2