The induced-proximity model, proposed by Guy S. Salvesen and Vishva M. Dixit, explains the mechanism of caspase activation in apoptosis. Caspases are a family of cysteine-dependent, Asp-specific proteases that play a crucial role in initiating and executing cell death. The model suggests that the first proteolytic signal in apoptosis is generated through the clustering of initiator caspase zymogens, such as caspase-8, mediated by adapter molecules like FADD. This clustering forces a high concentration of zymogens in a localized area, allowing for autoprocessing and activation. The induced-proximity model is supported by in vitro studies showing that caspase-8 zymogens can be processed and activated in the presence of FADD, and by in vivo experiments using artificial death switches. However, several questions remain, including the exact molecular mechanisms of autoprocessing, the role of dimerization, and the alignment of zymogens within the recruitment complex. The model highlights the importance of zymogenicity and the role of endogenous caspase inhibitors, such as IAPs, in regulating the apoptotic threshold.The induced-proximity model, proposed by Guy S. Salvesen and Vishva M. Dixit, explains the mechanism of caspase activation in apoptosis. Caspases are a family of cysteine-dependent, Asp-specific proteases that play a crucial role in initiating and executing cell death. The model suggests that the first proteolytic signal in apoptosis is generated through the clustering of initiator caspase zymogens, such as caspase-8, mediated by adapter molecules like FADD. This clustering forces a high concentration of zymogens in a localized area, allowing for autoprocessing and activation. The induced-proximity model is supported by in vitro studies showing that caspase-8 zymogens can be processed and activated in the presence of FADD, and by in vivo experiments using artificial death switches. However, several questions remain, including the exact molecular mechanisms of autoprocessing, the role of dimerization, and the alignment of zymogens within the recruitment complex. The model highlights the importance of zymogenicity and the role of endogenous caspase inhibitors, such as IAPs, in regulating the apoptotic threshold.