A systems biology analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation

Abstract

Background: Mathematical simulations of apoptosome formation and mechanisms of caspase-9 activation were conducted and validated against experimental data. Results: Only simulations that assume allosteric caspase-9 activation can accurately reproduce all experimental data. Conclusion: A mechanism of allosteric caspase-9 activation is favored over homodimerization-based activation. Significance: Our findings challenge the dogma that all initiator caspases are activated by homodimerization.