Editors' ChoiceApoptosis

Death by Integrins, Again

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Science's STKE  03 Jun 2003:
Vol. 2003, Issue 185, pp. tw210-TW210
DOI: 10.1126/stke.2003.185.tw210

A programmed cell death pathway has been proposed by Cardo-Vila that appears to connect the regulation of protein kinase C (PKC), the cytosolic protein annexin V, and αvβ5, a cell adhesion receptor that binds to extracellular matrix. A screen involving phage display led to the identification of a peptide that interacted specifically with the cytoplasmic tail of the β5 integrin subunit. With a peptide-specific antibody, the authors purified and identified annexin V from endothelial cell extracts. Annexin V is a cytosolic signaling protein that associates with and inhibits PKC. Intracellular delivery of the peptide into cultured endothelial cells caused apoptosis while the cells were still attached to extracellular matrix (in contrast, anoikis is a type of cell death that results from cell detachment). This effect was not observed in the absence of β5 expression. The peptide disrupted the β5 interaction with annexin V, but not the association of annexin V with PKC. The authors postulate that the peptide induces apoptosis by breaking a survival signaling pathway between integrins and PKC, thus allowing annexin V to inhibit PKC, which results in cell death.

M. Cardo-Vila, W. Arap, R. Pasqaulini, αvβ5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V. Mol. Cell 11, 1151-1162 (2003). [Online Journal]

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