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Abstract
This Open Question article highlights current advances in the study of non-apoptotic roles of apoptotic proteins. Apoptosis is a highly regulated and energy-requiring process in which cells actively kill themselves. Apoptosis helps remove extra cells to sculpt organs during embryo development and culls damaged cells throughout the body. Apoptosis relies on evolutionarily conserved proteins that include a family of proteases called caspases. Caspases activity has long been considered a hallmark of apoptosis. Yet an emerging body of literature indicates that caspase activity is required for a number of non-lethal processes that range from sculpting cells, removing protein aggregates, changing cell identity during differentiation or de-differentiation, and rebuilding tissues. Failure in each of these processes is associated with human disease. This article is not meant to be an exhaustive review but an introduction to the subject for an educated public, with caspases as a gateway example. I propose that it is time to explore non-apoptotic roles of caspases and other apoptotic proteins, in order to better understand their non-apoptosis function and to leverage new knowledge into new therapies.
Highlights
Active apical caspases cleave to activate effector caspases, which destroy non-caspase proteins to bring about apoptosis
A cell that went through anastasis suffers abnormalities such as chromosomal translocations and an increased propensity for oncogenic transformation, which occur in a caspase-dependent manner [13,15]
Caspase 3 activation was lower during red blood cells (RBCs) differentiation than if the same cells are exposed to an apoptotic stimulus, suggesting that quantitative differences in caspase activity may explain why RBC precursors survive and differentiate instead of die
Summary
Apoptosis is a process in which a cell commits suicide. It can last as long as a day and proceeds through recognizable steps. With results ranging from the removal of parts of a cell to completely altering its identity, much like turning a Victorian into a Tudor It is the remodelling of the cells using caspase activity that is attracting attention. Many questions remain such as how caspase activity is controlled to result in cellular remodelling instead of death and what the relevant substrates for the non-lethal roles of caspases are. It is by studying non-apoptotic roles of these conserved enzymes that we will reach a more complete understanding of the natural world and hope to identify new drug targets for a variety of human diseases. The examples discussed here focus instead on nonapoptotic roles of caspases, often with little information on how close cells came to apoptosis in each case
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