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MUC1 is a novel regulator of ErbB1 receptor trafficking

Oncogene volume 26, pages 1693–1701 (2007)Cite this article

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.

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Acknowledgements

We are grateful to Jean Wilson for helpful suggestions, Todd Camenisch, Jose Lopez, Jeanne Louderbough, Wendy Knowlton and Andrew Chang for a critical reading of this manuscript, and MA Hollingsworth for the MUC1 expression vector. FACS analysis was performed by the Flow Cytometry Shared Service of the Arizona Cancer Center. This work was supported by grants from the National Cancer Institute (JAS), the Susan Komen Breast Cancer Foundation (MRP), and the Department of Defense (RMB).

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  1. M R Pochampalli and R M el Bejjani: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Arizona Cancer Center and Bio5 Institute, University of Arizona, Tucson, AZ, USA

    M R Pochampalli, R M el Bejjani & J A Schroeder

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  1. M R Pochampalli
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  2. R M el Bejjani
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  3. J A Schroeder
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Correspondence to J A Schroeder.

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Pochampalli, M., Bejjani, R. & Schroeder, J. MUC1 is a novel regulator of ErbB1 receptor trafficking. Oncogene 26, 1693–1701 (2007). https://doi.org/10.1038/sj.onc.1209976

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