Lay summary
Programmed cell death (apoptosis) is required for normal development and homeostasis. Disruption of this process can result in diseases, including cancer, autoimmunity and degenerative disorders. 'Inhibitor of apoptosis' (IAP) proteins are key regulators of cell death and their misregulation contributes to tumour development and chemoresistance. Small molecule compounds that bind to IAPs are in clinical trials and show promise as novel drugs. However, their mode of action is uncertain.
Recent studies by the co-applicants and others show that the compounds inhibit signalling of membrane associated receptor complexes. Using purified proteins, we will determine how drug binding alters IAP function, and we will characterise IAP proteins and their complexes to determine how IAPs are recruited by membrane signalling complexes. This project will help indicate how IAPs are regulated and how this promising new class of therapeutic molecules functions. Together this knowledge will pave the way for the development of improved compounds.