EpCAM proteolysis: new fragments with distinct functions?

Ulrike Schnell, Jeroen Kuipers, Ben N. G. Giepmans*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    44 Citations (Scopus)
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    Abstract

    EpCAM [epithelial cell adhesion molecule; CD326 (cluster of differentiation 326)] is highly expressed on epithelium-derived tumours and can play a role in cell proliferation. Recently, RIP (regulated intramembrane proteolysis) has been implicated as the trigger for EpCAM-mediated proliferative signalling. However, RIP does not explain all EpCAM-derived protein fragments. To shed light on how proteolytic cleavage is involved in EpCAM signalling, we characterized the protein biochemically using antibodies binding to three different EpCAM domains. Using a newly generated anti-EpCAM antibody, we find that EpCAM can be cleaved at multiple positions within its ectodomain in addition to described peptides, revealing that EpCAM is processed via distinct proteolytic pathways. Here, we report on four new peptides, but also discuss the previously described cleavage products to provide a comprehensive picture of EpCAM cleavage at multiple positions. The complex regulation of EpCAM might not only result in the absence of full-length EpCAM, but the newly formed EpCAM-derived proteins may have their own signalling properties.

    Original languageEnglish
    Article numbere00030
    Pages (from-to)321-332
    Number of pages14
    JournalBioscience reports
    Volume33
    DOIs
    Publication statusPublished - 1-Apr-2013

    Keywords

    • cell-cell contact
    • EpCAM
    • notch-like signalling
    • regulated intramembrane proteolysis
    • polypeptides
    • shedding
    • AMYLOID PRECURSOR PROTEIN
    • REGULATED INTRAMEMBRANE PROTEOLYSIS
    • CELL ADHESION MOLECULE
    • ANTIGEN EP-CAM
    • LIPID RAFTS
    • SURFACE-ANTIGEN
    • CANCER-PATIENTS
    • EXPRESSION
    • CLEAVAGE
    • ECTODOMAIN

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