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Mechanism of action of isthmin on endothelial cells. On the left, ISM1 binds to integrin αvβ5 and triggers apoptosis via the recruitment and activation of caspase-8. On the right, ISM1 binds to cell surface GRP78 and is internalized via clathrin-mediated endocytosis. ISM1-GRP78 is then trafficked to mitochondria where it binds to AAC and induces apoptosis by interfering with ADP/ATP exchange.
