Biochemical processing of E-cadherin under cellular stress.
The proteolytic cleavage pathways of E-cadherin endogenously expressed in MDCK (Madin-Darby canine kidney) cells were characterized in cells treated with antimycin A and deoxyglucose to examine transmembrane protein processing under cellular stress. E-cadherin is a type I transmembrane protein which operates as the cell adhesion molecule component of the adherens junction, a complex of proteins involved in epithelial tissue development and integrity. We now demonstrate that treatment of MDCK cells with antimycin A and deoxyglucose activates caspase mediated pathways that cleave E-cadherin. E-cadherin is cleaved into two major fragments, with the sizes predicted by the location of a caspase-3 cleavage consensus sequence. Cleavage of E-cadherin and deposition of the C-terminal fragment into the cytoplasm are inhibited by the caspase inhibitor DEVD-CHO. Thus, a major mechanism for E-cadherin cleavage and dissolution of the adherens junction under antimycin/deoxyglucose treatment is caspase mediated, initiated by activation of an apoptosis pathway.
Keller
Steven H
SH
Department of Medicine, University of California, San Diego, CA 92103-8382, USA. shkeller@ucsd.edu
Nigam
Sanjay K
SK
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D001943:Breast Neoplasms; D015820:Cadherins / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D000900:Anti-Bacterial Agents; C495270:CTNNB1 protein, human; D015820:Cadherins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D003598:Cytoskeletal Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D015534:Trans-Activators; C108637:aspartyl-glutamyl-valyl-aspartal; D051176:beta Catenin; D000968:Antimycin A; D003847:Deoxyglucose; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases