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Sci. STKE, 6 November 2001
Vol. 2001, Issue 107, p. tw412
[DOI: 10.1126/stke.2001.107.tw412]

EDITORS' CHOICE

Apoptosis Bound to Survive

Many cells require attachment for survival. However, even cells growing attached to other cells and in the presence of an extracellular matrix without apparent stress or injury will undergo apoptosis. Stupack et al. show that when cells expressing particular integrins grow on adhesive surfaces that lack the appropriate integrin ligand, unligated integrins result, and that can stimulate apoptosis. The proapoptotic activity of unligated integrins was found to reside in the cytosolic domains of the β subunits, specifically the β1 and β3 subunits. However, apoptotic activity required membrane association, because expression of fusion proteins that lacked a transmembrane domain did not stimulate apoptosis, whereas expression of fusion proteins with transmembrane domains or the native β subunits did. The minimal region that stimulates apoptosis does not contain any of the known domains responsible for integrin signaling. In cells undergoing integrin-mediated cell death due to the expression of unligated β chimeras or β subunits, caspase-8 colocalized with the unligated proteins and was activated. Thus, the β subunit of unligated integrins appears to promote apoptosis through the recruitment of activated caspase-8. This places the at least the β1- and β3-containing integrins in the family of "dependence" receptors that can stimulate cell survival when bound and cell death when unbound.

D. G. Stupack, X. S. Puente, S. Boutsaboualoy, C. M. Storgard, D. A. Cheresh, Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. J. Cell Biol. 155, 459-470 (2001). [Abstract] [Full Text]

Citation: Bound to Survive. Sci. STKE 2001, tw412 (2001).


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