It is during this phase that the cell integrates multiple signals that will lead to the initiation of cell death. Receptor ligation leads directly to activation of caspases. My lab is interested in molecules that control the balance of these signals. A20 is a protein that shifts the balance in favor of protection. We are currently defining the molecular target of A20.
Results indicate that it acts at the level of the signalsome.
Homology searches have revealed that A20 represents a whole class of proteins conserved between Drosophila and mammals. The lab is currently cloning and characterizing these A20 homologues. This gene, Boo, is exclusively expressed in the ovaries and we are investigating the role of the gene product in ovarian development and malignancies. The commitment phase can involve synthesis of new pro-apoptotic genes. A good example for such a process is Glucocorticoid induced cell death in T cells.