Scientists unlock secret of death protein’s activation

Scientists at Dana-Farber Cancer Institute have identified a previously undetected trigger point on a naturally occurring “death protein” that helps the body get rid of unwanted or diseased cells. They say it may be possible to exploit the newly found trigger as a target for designer drugs that would treat cancer by forcing malignant cells to commit suicide.

Loren Walensky, MD, PhD, pediatric oncologist and chemical biologist at Dana-Farber and Children’s Hospital Boston, and colleagues report in the Oct. 23 issue of the journal Nature that they directly activated this trigger on the “executioner” protein BAX, killing laboratory cells by setting in motion their self-destruct mechanism.

The researchers fashioned a peptide (a protein subunit) that precisely matched the shape of the newly found trigger site on the killer protein, which lies dormant in the cell’s interior until activated by cellular stress. When the peptide docked into the binding site, BAX was spurred into assassin mode. The activated BAX proteins flocked to the cell’s power plants, the mitochondria, where they poked holes in the mitochondria’s membranes, killing the cells. This process is called apoptosis, or programmed cell death.

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