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The Adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes

Carolina Mendoza-Topaz1, Juliusz Mieszczanek, Mariann Bienz

  • 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

Open Biology
|May 31, 2012
PubMed

Insights

Adenomatous polyposis coli (APC) protein is crucial for colorectal cancer suppression by enabling Axin protein assembly. APC prevents Axin inactivation by Dishevelled, thus maintaining Wnt signaling control.

Area of Science:

  • Molecular biology
  • Cell biology
  • Cancer research

Background:

  • Colorectal cancer often involves Adenomatous polyposis coli (APC) tumor suppressor inactivation.
  • APC normally downregulates Wnt signaling by promoting the degradation of β-catenin (Armadillo) via Axin.
  • Axin's DIX domain facilitates polymerization into degradasomes, essential for β-catenin degradation.

Purpose of the Study:

  • To elucidate the mechanism by which APC promotes Axin function in Wnt signaling.
  • To investigate the role of APC in Axin degradasome assembly and stability.
  • To understand how APC prevents Axin inactivation by Dishevelled.

Main Methods:

  • Utilized apc null mutant Drosophila tissues to study Axin degradasome assembly.
  • Examined APC mutant cancer cells for alterations in degradasome assembly.
  • Performed co-expression experiments to analyze the interaction between APC, Axin, and Dishevelled.

Main Results:

  • APC is essential for Axin degradasome assembly, which is required for Armadillo downregulation.
  • Degradasome assembly is impaired in APC-mutant cancer cells.
  • APC prevents Axin from interacting with Dishevelled, thereby inhibiting signalosome formation and maintaining degradasome function.

Conclusions:

  • APC facilitates Axin's self-assembly into degradasomes through its DIX domain.
  • APC opposes the Dishevelled-mediated inactivation of Axin, ensuring proper Wnt signaling regulation.
  • APC's dual role in promoting degradasome formation and preventing signalosome formation is critical for its tumor suppressor function in colorectal cancer.
Keywords:
APC tumour suppressor, Axin degradasome, Dishevelled signalosome

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