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Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon

B Rubinfeld1, D A Tice, P Polakis

  • 1Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.

The Journal of Biological Chemistry
|August 7, 2001
PubMed

Insights

Axin and adenomatous polyposis coli protein (APC) regulate beta-catenin. Introducing an axin-binding site into APC conferred regulatory activity and induced hyperphosphorylation, suggesting CKIepsilon mediates APC function.

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Oncogenesis

Background:

  • Axin and adenomatous polyposis coli (APC) protein form a complex that down-regulates beta-catenin.
  • Beta-catenin is a proto-oncogene implicated in various cancers.

Purpose of the Study:

  • To investigate the role of axin-binding sites in APC function.
  • To elucidate the mechanism of axin-dependent APC phosphorylation and its effect on beta-catenin regulation.

Main Methods:

  • Transposition of an axin-binding site into an APC fragment.
  • Coexpression of proteins and analysis of phosphorylation.
  • Site-directed mutagenesis of APC serine residues.

Main Results:

  • Transposition of an axin-binding site conferred beta-catenin regulatory activity to an APC fragment.
  • The modified APC fragment underwent hyperphosphorylation upon coexpression with axin, mediated by casein kinase 1epsilon (CKIepsilon).
  • Mutations in APC serine residues impaired axin-dependent phosphorylation and beta-catenin regulation.

Conclusions:

  • Axin-dependent phosphorylation of APC, partly mediated by CKIepsilon, is crucial for regulating APC's function in beta-catenin control.
  • This mechanism highlights a key pathway in the regulation of beta-catenin, with implications for cancer research.

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