title: EpCAM proteolysis: new fragments with distinct functions?
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.
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands.
authors: Ulrike
authors: U
authors: Schnell
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands.
authors: Jeroen
authors: J
authors: Kuipers
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands.
authors: Ben N G
authors: BN
authors: Giepmans
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule