MUC1 is a novel regulator of ErbB1 receptor trafficking.
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.
Pochampalli
M R
MR
Department of Molecular and Cellular Biology, Arizona Cancer Center and Bio5 Institute, University of Arizona, Tucson, AZ 85724, USA.
el Bejjani
R M
RM
Schroeder
J A
JA
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D018396:Mucin-1 / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D025801:Ubiquitin / Q000378:metabolism
D017931:DNA Primers; D018396:Mucin-1; D025801:Ubiquitin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors