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

Austin T Baldwin; Bryan T Phillips

doi:10.1242/jcs.146514

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

Journal article

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Peer reviewed

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

Austin T Baldwin and Bryan T Phillips

Journal of cell science, Vol.127(Pt 12), pp.2771-2781

06/15/2014

DOI: 10.1242/jcs.146514

PMCID: PMC6518273

PMID: 24762815

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Abstract

The APC tumor suppressor regulates diverse stem cell processes including gene regulation through Wnt-β-catenin signaling and chromosome stability through microtubule interactions, but how the disparate functions of APC are controlled is not well understood. Acting as part of a Wnt-β-catenin pathway that controls asymmetric cell division, Caenorhabditis elegans APC, APR-1, promotes asymmetric nuclear export of the β-catenin WRM-1 by asymmetrically stabilizing microtubules. Wnt function also depends on a second β-catenin, SYS-1, which binds to the C. elegans TCF POP-1 to activate gene expression. Here, we show that APR-1 regulates SYS-1 levels in asymmetric stem cell division, in addition to its known role in lowering nuclear levels of WRM-1. We demonstrate that SYS-1 is also negatively regulated by the C. elegans homolog of casein kinase 1α (CKIα), KIN-19. We show that KIN-19 restricts APR-1 localization, thereby regulating nuclear WRM-1. Finally, the polarity of APR-1 cortical localization is controlled by PRY-1 (C. elegans Axin), such that PRY-1 controls the polarity of both SYS-1 and WRM-1 asymmetries. We propose a model whereby Wnt signaling, through CKIα, regulates the function of two distinct pools of APC - one APC pool negatively regulates SYS-1, whereas the second pool stabilizes microtubules and promotes WRM-1 nuclear export.

Protein Kinases - metabolism

Adenomatous Polyposis Coli Protein - physiology

Cell Polarity

Caenorhabditis elegans - metabolism

Caenorhabditis elegans - genetics

Cytoskeletal Proteins - genetics

Asymmetric Cell Division

Caenorhabditis elegans Proteins - metabolism

Transcription Factors - genetics

Cell Nucleus - physiology

Protein Transport

Transcription Factors - metabolism

Microtubules - metabolism

Animals

Caenorhabditis elegans - cytology

Cytoskeletal Proteins - metabolism

Stem Cells - physiology

Caenorhabditis elegans Proteins - physiology

Active Transport, Cell Nucleus

Caenorhabditis elegans Proteins - genetics

Wnt Signaling Pathway

Details

Title: Subtitle: The tumor suppressor APC differentially regulates multiple β-catenins through the function of axin and CKIα during C. elegans asymmetric stem cell divisions
Creators: Austin T Baldwin - Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA
Bryan T Phillips - Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA bryan-phillips@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.127(Pt 12), pp.2771-2781
DOI: 10.1242/jcs.146514
PMID: 24762815
PMCID: PMC6518273
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 06/15/2014
Academic Unit: Biology
Record Identifier: 9984083841502771

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