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The tumor suppressor APC differentially regulates multiple β-catenins through the function of axin and CKIα during C.

Austin T Baldwin1, Bryan T Phillips2

  • 1Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA.

Journal of Cell Science
|April 26, 2014
PubMed

Insights

The Adenomatous Polyposis Coli (APC) tumor suppressor controls stem cell division by regulating two beta-catenin proteins. This study reveals how APC

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Adenomatous Polyposis Coli (APC) tumor suppressor is crucial for stem cell regulation, impacting gene expression and chromosome stability.
  • APC's diverse functions, particularly in Wnt-β-catenin signaling and microtubule interactions, are not fully understood.
  • In Caenorhabditis elegans, APC (APR-1) regulates asymmetric cell division by controlling β-catenin WRM-1 nuclear export via microtubule stabilization.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling the disparate functions of APC in stem cell division.
  • To investigate the role of APR-1 in regulating the second β-catenin, SYS-1, during asymmetric cell division.
  • To understand how casein kinase 1α (CKIα) and Axin (PRY-1) influence APC function and polarity.

Main Methods:

  • Utilized the model organism Caenorhabditis elegans.
  • Investigated protein-protein interactions and localization dynamics.
  • Employed genetic manipulation to study gene and protein functions.

Main Results:

  • APR-1 was found to regulate SYS-1 levels in asymmetric stem cell division, in addition to its role in WRM-1 nuclear export.
  • The C. elegans casein kinase 1α homolog, KIN-19, negatively regulates SYS-1 and restricts APR-1 localization, impacting WRM-1 levels.
  • PRY-1 (Axin) controls the cortical localization polarity of APR-1, thereby regulating the asymmetry of both SYS-1 and WRM-1.

Conclusions:

  • A model is proposed where Wnt signaling, mediated by CKIα, differentially regulates two APC pools.
  • One APC pool negatively regulates SYS-1, while a second pool stabilizes microtubules and promotes WRM-1 nuclear export.
  • This dual regulation by APC ensures proper control of gene expression and chromosome stability during asymmetric stem cell division.
Keywords:
APCC. elegansSYS-1WRM-1Wntβ-catenin

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