Suppression of kinesin expression disrupts adenomatous polyposis coli (APC) localization and affects beta-catenin turnover in young adult mouse colon (YAMC) epithelial cells.
Mutational inactivation of the adenomatous polyposis coli (APC) protein initiates most hereditary and sporadic colon cancers. The tumor-suppressive effect of APC is mediated by promoting degradation of the oncogenic transcriptional activator beta-catenin, and loss of APC function often results in nuclear accumulation of beta-catenin in cancer cells. APC is a nuclear-cytoplasmic shuttling protein and moves along microtubules in the cytoplasm. However, the molecular motor proteins responsible for APC translocation and the implications of APC trafficking on beta-catenin turnover are unknown. Here we show that APC protein is associated with microtubules and is colocalized with kinesin heavy chain (KHC) and beta-catenin to clusters of puncta at the tip regions of cellular extensions in a conditionally immortalized mouse colon epithelial cell line, young adult mouse colon (YAMC, APC+/+). Inhibition of KHC expression using an antisense oligonucleotide disrupts peripheral translocation of APC and induces nucleocytoplasmic accumulation of beta-catenin. These data indicate that KHC-mediated APC translocation is tightly coordinated with beta-catenin turnover in the cell.
Cui
Hongyi
H
Center for Molecular Medicine, University of Conneticut Health Center, Farmington 06030, USA.
Dong
Mei
M
Sadhu
Devaki N
DN
Rosenberg
Daniel W
DW
D021581:Active Transport, Cell Nucleus; D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D003106:Colon / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D016547:Kinesins