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. 1999 Feb 11;397(6719):534-9.
doi: 10.1038/17409.

RGD peptides induce apoptosis by direct caspase-3 activation

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RGD peptides induce apoptosis by direct caspase-3 activation

C D Buckley et al. Nature. .

Abstract

Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis.

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Comment in

  • New way to activate caspases.
    Ruoslahti E, Reed J. Ruoslahti E, et al. Nature. 1999 Feb 11;397(6719):479-80. doi: 10.1038/17229. Nature. 1999. PMID: 10028964 No abstract available.

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