Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model

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P R Rao1, K Makhijani, L S Shashidhara

  • 1Centre for Cellular and Molecular Biology, Hyderabad, India. prashanth21676@gmail.com

Oncogene
|October 31, 2007
PubMed

Insights

Adenomatous polyposis coli (APC) binds beta-catenin independently of GSK-3beta phosphorylation. This binding sequesters beta-catenin, rendering it non-functional and suppressing Wnt/Wingless pathway activation.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Conflicting reports exist regarding the necessity of GSK-3beta-mediated phosphorylation for APC's interaction with beta-catenin.
  • The precise mechanism by which APC regulates beta-catenin stability and function remains under investigation.

Purpose of the Study:

  • To investigate the role of GSK-3beta phosphorylation in the binding and functional regulation of beta-catenin by APC.
  • To clarify the relationship between APC, beta-catenin, and the Wnt/Wingless signaling pathway.

Main Methods:

  • Utilized a Drosophila model with genetic manipulation of Shaggy/GSK-3beta (loss-of-function) and human APC (gain-of-function).
  • Observed the effects of misexpressed human APC on Armadillo/beta-catenin binding and Wnt/Wingless pathway phenotypes.

Main Results:

  • Misexpressed human APC effectively sequestered Armadillo/beta-catenin in Drosophila.
  • Human APC suppressed Wnt/Wingless phenotypes that arise from Shaggy/GSK-3beta loss-of-function.
  • These findings suggest that sequestered beta-catenin is functionally inactive.

Conclusions:

  • APC-mediated binding of beta-catenin does not necessitate prior phosphorylation by GSK-3beta.
  • APC binding is sufficient to sequester beta-catenin and inhibit its function, independent of GSK-3beta activity.

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