Suppression of kinesin expression disrupts adenomatous polyposis coli (APC) localization and affects beta-catenin turnover in young adult mouse colon (YAMC) epithelial cells

Exp Cell Res. 2002 Oct 15;280(1):12-23. doi: 10.1006/excr.2002.5506.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenomatous Polyposis Coli Protein / analysis*
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Cell Line, Transformed
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cell Polarity
  • Cells, Cultured
  • Colon / chemistry*
  • Colon / cytology
  • Colon / metabolism*
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Epithelial Cells / chemistry
  • Epithelial Cells / metabolism
  • Genes, Tumor Suppressor
  • Kinesin / metabolism*
  • Mice
  • Microtubules / physiology
  • Nuclear Proteins / metabolism
  • Protein Transport
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • beta Catenin


  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
  • Kinesin