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Molecular and Cellular Biochemistry

, Volume 274, Issue 1–2, pp 63–67 | Cite as

CK2 as a positive regulator of Wnt signalling and tumourigenesis

  • David C. SeldinEmail author
  • Esther Landesman-Bollag
  • Marganit Farago
  • Nicolas Currier
  • David Lou
  • Isabel Dominguez
Article

Abstract

CK2 is upregulated in rapidly dividing cells including most human tumours. Transgenic overexpression of CK2 in lymphoid or mammary lineages predisposes to transformation. Multiple signalling and oncogene pathways could be regulated by CK2 in this process. Our studies suggest that phosphorylation of critical oncogenes by CK2, as well as by other serine-threonine kinases, regulates their stability via susceptibility to the proteasomal degradation system. β-catenin is a transcriptional co-factor in the Wnt signalling pathway that is regulated in this fashion. Inactivating mutations in the adenomatosis polyposis coli (APC) gene, which encodes a carrier protein for β-catenin, or stabilizing mutations in β-catenin itself, frequently occur in human tumours. CK2 and the monomeric serine-threonine kinase GSK3 have opposing actions on β-catenin: GSK-3 phosphorylation of the N-terminus of β-catenin promotes degradation; while phosphorylation by CK2 in the armadillo repeat protein interaction domain protects it. β-catenin is overexpressed in mammary tumours occurring in mice transgenic for CK2 or a dominant negative form of GSK3, and also in mammary tumours arising following treatment with the environmental carcinogen DMBA. Experiments are underway to determine whether expression of both CK2 and kinase inactive GSK3 further accelerates tumorigenesis. Inhibitors of GSK3 under development for treatment of diabetes could promote tumours, while CK2 inhibitors should be useful agents for treatment of cancer.

Keywords

breast cancer casein kinase II glycogen synthase kinase 3 GSK3 protein kinase CK2 Wnt signalling 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • David C. Seldin
    • 1
    • 2
    Email author
  • Esther Landesman-Bollag
    • 1
  • Marganit Farago
    • 1
  • Nicolas Currier
    • 1
  • David Lou
    • 1
  • Isabel Dominguez
    • 1
  1. 1.Section of Hematology–Oncology, Department of MedicineBoston University Medical CenterBostonUSA
  2. 2.BostonUSA

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