PROTEIN INTERACTIONS IN APOPTOSIS

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Programmed cell death (PCD) and apoptosis are important processes of self-renewing tissues. When this normal regulatory system is disrupted, the results can contribute to several diseases including cancer. Therefore the apoptotic pathway offers an intriguing avenue to intervene in the pathogenesis of the disease. The Bcl-2 family of proteins are critical regulatory molecules that either promote or repress the cell death pathway through a complex pattern of protein-protein interactions. We have crystallized a protein BAG-1 that binds to Bcl-2, and enhances the anti-apoptotic activity of Bcl-2. The goal is to understand the molecular basis for the protein associations in apoptosis and to generate atomic models to reveal interacting surfaces and/or conformational changes that may serve as molecular triggers in the apoptotic response.