Inhibitor of Apoptosis Proteins and Caspases

Inhibitors of apoptosis proteins (IAPs) were first identified as insect viral proteins that block host cell apoptosis. Cellular homologs bearing the characteristic baculoviral IAP repeat (BIR) domain have now been found in all metazoans and have more diverse functions than their name suggests. Some cellular IAPs do, in fact, inhibit apoptosis, in part at least by directly inhibiting cysteine proteases, called caspases, that are ultimately responsible for killing a cell. The primary aim of this chapter is to explore the intricate regulation of caspases by IAPs, and the exquisite counter regulation of IAPs by antagonist proteins. Interest in IAPs extends beyond apoptosis pathways and recent evidence suggests that IAPs modulate cell-signaling pathways that affect growth and proliferation and some of these remarkable studies will be discussed.