Nuclear association of the cytoplasmic tail of MUC1 and β-catenin

Yunfei Wen, Thomas C. Caffrey, Margaret J. Wheelock, Keith R. Johnson, Michael A. Hollingsworth

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

MUC1, an integral membrane mucin associated with the metastatic phenotype, is overexpressed by most human carcinoma cells. The MUC1 cytoplasmic tail (CT) is postulated to function in morphogenetic signal transduction via interactions with Grb2/Sos, c-Src, and β-catenin. We investigated intracellular trafficking of the MUC1 CT, using epitope-tagged constructs that were overexpressed in human pancreatic cancer cell lines S2-013 and Panc-1. The MUC1 CT was detected at the inner cell surface, in the cytosol, and in the nucleus of cells overexpressing MUC1. Fragments of the MUC1 CT were associated with β-catenin in both cytoplasm and nuclei. Overexpression of MUC1 increased steady state levels of nuclear β-catenin but decreased nuclear levels of plakoglobin (γ-catenin). There was no detectable association between plakoglobin and the MUC1 CT. Coimmunoprecipitation experiments revealed that the cytoplasmic and nuclear association of MUC1 CT and β-catenin was not affected by disruption of Ca2+-dependent intercellular cadherin interactions. These results demonstrate nuclear localization of fragments of MUC1 CT in association with β-catenin and raise the possibility that overexpression of the MUC1 CT stabilizes β-catenin and enhances levels of nuclear β-catenin during disruption of cadherin-mediated cell-cell adhesion.

Original languageEnglish (US)
Pages (from-to)38029-38039
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number39
DOIs
StatePublished - Sep 26 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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