MUC1 is a novel regulator of ErbB1 receptor trafficking

M. R. Pochampalli, R. M El Bejjani, Joyce Schroeder

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

ErbB receptors are key regulators of cell survival and growth in normal and transformed tissues. The oncogenic glycoprotein MUC1 is a binding partner and substrate for erbB1 and MUC1 expression can potentiate erbB-dependent signal transduction. After receptor activation, erbB1 is typically downregulated via an endocytic pathway that results in receptor degradation or recycling. We report here that MUC1 expression inhibits the degradation of ligand-activated erbB1. Through the use of both RNAi-mediated knock down and overexpression constructs of MUC1, we show that MUC1 expression inhibits erbB1 degradation after ligand treatment in breast epithelial cells. This MUC1-mediated protection against erbB1 degradation can increase total cellular pools of erbB1 over time. Biotinylation of surface proteins demonstrates that cell-surface associated erbB1 receptor is protected by MUC1 against ligand-induced degradation, although this is accompanied by an increase in erbB1 internalization. The MUC1-mediated protection against degradation occurs with a decrease in EGF-stimulated ubiquitination of erbB1, and an increase in erbB1 recycling. These data indicate that MUC1 expression is a potent regulator of erbB1 receptor stability upon activation and may promote transformation through the inhibition of erbB1 degradation.

Original languageEnglish (US)
Pages (from-to)1693-1701
Number of pages9
JournalOncogene
Volume26
Issue number12
DOIs
StatePublished - Mar 15 2007

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Recycling
Ligands
Membrane Proteins
Biotinylation
Ubiquitination
RNA Interference
Epidermal Growth Factor
Signal Transduction
Cell Survival
Glycoproteins
Breast
Down-Regulation
Epithelial Cells
Growth
ErbB Receptors

Keywords

  • Breast cancer
  • ErbB1
  • MUC1
  • Phosphorylation
  • Ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

MUC1 is a novel regulator of ErbB1 receptor trafficking. / Pochampalli, M. R.; Bejjani, R. M El; Schroeder, Joyce.

In: Oncogene, Vol. 26, No. 12, 15.03.2007, p. 1693-1701.

Research output: Contribution to journalArticle

Pochampalli, M. R. ; Bejjani, R. M El ; Schroeder, Joyce. / MUC1 is a novel regulator of ErbB1 receptor trafficking. In: Oncogene. 2007 ; Vol. 26, No. 12. pp. 1693-1701.
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