RRC ID 45686
著者 Baldwin AT, Phillips BT.
タイトル The tumor suppressor APC differentially regulates multiple β-catenins through the function of axin and CKIα during C. elegans asymmetric stem cell divisions.
ジャーナル J Cell Sci
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.
巻・号 127(Pt 12)
ページ 2771-81
公開日 2014-6-15
DOI 10.1242/jcs.146514
PII jcs.146514
PMID 24762815
PMC PMC6518273
MeSH Active Transport, Cell Nucleus Adenomatous Polyposis Coli Protein / physiology* Animals Asymmetric Cell Division Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caenorhabditis elegans Proteins / physiology* Cell Nucleus / physiology Cell Polarity Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Microtubules / metabolism Protein Kinases / metabolism* Protein Transport Stem Cells / physiology Transcription Factors / genetics Transcription Factors / metabolism* Wnt Signaling Pathway
IF 4.573
引用数 21
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm514