Understanding the molecular secrets of apoptosis, or programmed cell suicide, they say, will enable scientists to identify potential drug targets against these diseases. Reporting the results of a study March 1 in the journal Nature, Emad Alnemri, Ph.D., professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his co-workers at Princeton University and the University of Pittsburgh describe a particular molecular pathway involved in apoptosis. Scientists believe apoptosis gone awry underlies neurodegenerative diseases, autoimmune diseases such as lupus, and cancer. In the study, the researchers explain how two similar proteins compete for control of a cell's ability to die at a preset time. The Jefferson team focused on an enzyme, caspase-9, which Dr. Alnemri's group discovered.
Caspases are cellular enzymes that bring about apoptosis.
Other proteins in the cell known as inhibitors of apoptosis, or IAPs, block caspase activity, preventing cells from dying. The scientists discovered how a region in the XIAP protein called BIR3 attaches to caspase-9 and blocks its activity. Harnessing Smac's activity or devising a drug to mimic it allows caspase activation and apoptosis to occur. Our study defines how XIAP blocks caspase-9 activity, a first step in designing and improving the efficacy of new drugs to inhibit or activate caspases. You want to activate apoptosis by activating caspases in cancer to kill the cells.